Phosphonate nucleotide compounds

ABSTRACT

A phosphonate nucleotide compound having antiviral activity and is useful for an orally available and highly safe antiviral agent, which is represented by the following formula (I): ##STR1## wherein R 1  represents hydrogen, a C 1  -C 6  alkoxy, a halogen-substituted C 1  -C 4  alkoxy, halogen, amino, or nitro; R 2  and R 3  independently represent hydrogen, a C 1  -C 22  alkyl, an acyloxymethy, an acylthioethyl, or a halogen-substituted ethyl; R 4  represents hydrogen, a C 1  -C 4  alkyl, a C 1  -C 4  hydroxyalkyl, or a halogen-substituted C 1  -C 4  alkyl; and X represents carbon or nitrogen.

FIELD OF THE INVENTION

The present invention relates to novel phosphonate nucleotide compounds. More specifically, the present invention relates to phosphonate nucleotide compounds and their salts, and hydrates and solvates thereof, which have antiviral activity and are useful as medicaments.

BACKGROUND OF THE INVENTION

Viral Infectious diseases are recognized as serious clinical problems. In order to therapeutically treat such diseases, attempts have been made to develop medicaments having antiviral activity, while exhibiting no growth inhibitory activity against normal cells systems. For example, extensive recent researches has been focused on phosphonate nucleotides as selective antiviral agents. More specifically, 9-(2-phosphonylmethoxy) ethyladenine (PMEA), 9-(2-phosphonylmethoxy)ethyl-2,6-diaminopurine (PMDAP) and the like are reported as being effective against herpes simplex type 1 and 2 viruses (HSV-1 and HSV-2), human immunodeficiency virus (HIV), and human hepatitis B virus (HBV) (Yokota et al., Antimicrob. Agents Chemother., 35, 394, 1991; Votruba et al., Mol. Pharmacol., 32, 524, 1987).

However, these known phosphonate nucleotides have problems of insufficient safety because they have toxicities against living bodies, whose typical example includes bone marrow cell growth inhibition, and have potential mutagenicities (Antiviral Research, 16, 77, 1991). In addition, there is another problem that they are not orally absorbable (De Clercq et al., Antimicrob. Agents Chemother., 33, 185, 1989), and their administration routes are limited to parenteral routes such as intravenous or intramuscular injection to achieve blood concentrations essential for exhibiting pharmacological effects. Therapeutic treatment by parenteral administration can hardly be carried out for patients other than inpatients, and is not preferably applied to treatments of AIDS, hepatitis B virus infection and the like which require long-term care.

The inventors of the present invention found that particular ester derivatives of phosphonate nucleotides have high oral absorbability (EP 632,048 A1). However, they have not yet been clinically developed.

SUMMARY OF THE INVENTION

An object of the present invention is to provide an antiviral agent having no toxicity such as growth inhibition against bone marrow cells or mutagenicity. Another object of the present invention is to provide an antiviral agent having excellent oral absorbability.

The inventors of the present invention conducted various studies to achieve the foregoing objects, and as a result, they found that particular 2-amino-6-arylthiopurinephosphonates, which are not specifically disclosed in the aforementioned EP 632,048 A1, have high antiviral activities, and that these compounds are safer to living bodies than conventionally proposed compounds and have excellent oral absorbability. The present invention was achieved on the basis of these findings.

The present invention thus provides phosphonate nucleotide compounds represented by the following formula (I) and their salts, and hydrates and solvates thereof: ##STR2## wherein R¹ represents hydrogen atom, a C₁ -C₆ alkoxy group, a C₁ -C₄ alkoxy group substituted with one or more halogen atoms, a halogen atom, amino group, or nitro group; R² and R¹ independently represent hydrogen atom, a C₁ -C₂ 2 alkyl group, an acyloxymethyl group, an acylthioethyl group, or an ethyl group substituted with one or more halogen atoms; R⁴ represents hydrogen atom, a C₁ -C₄ alkyl group, a C₁ -C₄ hydroxyalkyl group, or a C₁ -C₄ alkyl group substituted with one or more halogen atoms; and X represents a carbon atom or a nitrogen atom.

According to another aspect of the present invention, there are provided a pharmaceutical composition comprising a substance selected from the group consisting of the aforementioned compound and its salt, and a hydrate and a solvate thereof together with a pharmaceutically acceptable additive; and an antiviral agent comprising as an active ingredient a substance selected from the group consisting of the aforementioned compound and its salt, and a hydrate and a solvate thereof.

According to further aspect of the present invention, there are provided a use of a substance selected from the group consisting of the aforementioned compound and its salt, and a hydrate and a solvate thereof for the manufacture of the aforementioned pharmaceutical composition; and a method for therapeutic treatment of a viral infectious disease which comprises a step of administering to a mammal including a human an effective amount of a substance selected from the group consisting of the aforementioned compound and its salt, and a hydrate and a solvate thereof.

DETAILED EXPLANATION OF PREFERRED EMBODIMENTS OF THE INVENTION

In the phosphonate nucleotide compounds of the above general formula (I), examples of the C₁ -C₆ alkoxy group represented by R¹ include methoxy group, ethoxy group, n-propoxy group, isopropoxy group, n-butoxy group, isobutoxy group, sec-butoxy group, tert-butoxy group, n-pentyloxy group, and n-hexyloxy group. Examples of the C₁ -C₄ alkoxy group substituted with one or more halogen atoms represented by R¹ include monofluoromethoxy group, difluoromethoxy group, trifluoromethoxy group, monofluoroethoxy group, difluoroethoxy group, trifluoroethoxy group, tetrafluoroethoxy group, pentafluoroethoxy group, monofluoropropoxy group, difluoropropoxy group, trifluoropropoxy group, tetrafluoropropoxy group, pentafluoropropoxy group, hexafluoropropoxy group, heptafluoropropoxy group, monofluoroisopropoxy group, difluoroisopropoxy group, trifluoroisopropoxy group, tetrafluoroisopropoxy group, pentafluoroisopropoxy group, hexafluoroisopropoxy group, and heptafluoroisopropoxy group.

Examples of the C₁ -C₂ 2 alkyl group represented by R² and R³ include methyl group, ethyl group, n-propyl group, isopropyl group, n-butyl group, isobutyl group, sec-butyl group, tert-butyl group, pentyl group, hexyl group, heptyl group, octyl group, nonyl group, decyl group, undecyl group, dodecyl group, tridecyl group, tetradecyl group, pentadecyl group, hexadecyl group, heptadecyl group, octadecyl group, nonadecyl group, eicosyl group, heneicosyl group, and docosyl group. Examples of the acyloxymethyl group represented by R² and R³ include acetyloxymethyl group, propionyloxymethyl group, butyryloxymethyl group, isobutyryloxymethyl group, valeryloxymethyl group, isovaleryloxymethyl group, and pivaloyloxymethyl group.

Examples of the acylthioethyl group represented by R² and R³ include acetylthioethyl group, propionylthioethyl group, butyrylthioethyl group, isobutyrylthioethyl group, valerylthioethyl group, isovalerylthioethyl group, and pivaloylthioethyl. In the ethyl groups substituted with one or more halogen atoms represented by R² and R³, the sort of halogen atoms may be any of fluorine atoms, chlorine atoms, bromine atoms, or iodine atoms. Examples of the ethyl group substituted with one or more halogen atoms include 1-fluoroethyl group, 2-fluoroethyl group, 1-chloroethyl group, 2-chloroethyl group, 2-bromoethyl group, 2,2-difluoroethyl group, 2,2-dichloroethyl group, 2,2-dibromoethyl group, 2,2,2-trifluoroethyl group, 2,2,2-trichloroethyl group, and 2,2,2-tribromoethyl group. In particular, the substitutions at 2-position of the ethyl groups are preferred, and fluorine atom is preferred among the halogen atoms. It is preferred that at least one of R² and R³ is an ethyl group substituted with one or more halogen atoms, particularly 2,2,2-trifluoroethyl group.

Examples of the C₁ -C₄ alkyl group represented by R⁴ include methyl group, ethyl group, n-propyl group, isopropyl group, n-butyl group, isobutyl group, sec-butyl group, and tert-butyl group. Examples of the C₁ -C₄ hydroxyalkyl group represented by R⁴ include hydroxymethyl group, 1-hydroxyethyl group, 2-hydroxyethyl group, 1-hydroxypropyl group, 2-hydroxypropyl group, 3-hydroxypropyl group, 1-hydroxybutyl group, 2-hydroxybutyl group, 3-hydroxybutyl group, and 4-hydroxybutyl group. Examples of the C₁ -C₄ alkyl group substituted with one or more halogen atoms represented by R⁴ include methyl group, ethyl group, n-propyl group, isopropyl group, n-butyl group, isobutyl group, sec-butyl group, and tert-butyl group which are substituted with one or more halogen atoms such as fluorine atoms and chlorine atoms. More specifically, examples include fluoromethyl group, difluoromethyl group, trifluoromethyl group, fluoroethyl group, chloroethyl group, fluoropropyl group, chloropropyl group, fluorobutyl group, and chlorobutyl group.

According to the present invention, the first condition for preferred compounds includes that R¹ is hydrogen atom or a C₁ -C₆ alkoxy group. The second condition for preferred compounds includes that R¹ is hydrogen atom or a C₁ -C₆ alkoxy group; and R² and R³ are independently selected from hydrogen atom, a C₁ -C₂ 2 alkyl group, or ethyl group substituted with one or more halogen atoms. In addition, the third condition for preferred compounds includes that R¹ is hydrogen atom or a C₁ -C₄ alkoxy group; R² and R³ are independently selected from hydrogen atom, a C₁ -C₂ 2 alkyl group, or 2,2,2-trifluoroethyl group; and R⁴ is hydrogen atom or methyl group. The fourth condition for preferred compounds includes that R¹ is hydrogen atom or a C₁ -C₄ alkoxy group; R² and R³ are independently selected from hydrogen atom or 2,2,2-trifluoroethyl group; and R⁴ is hydrogen atom or methyl group.

Examples of the preferred compounds satisfying the aforementioned conditions include the following compounds:

2-amino-9- 2- bis(2,2,2-trifluoroethyl)phosphonylmethoxy!ethyl!-6-phenylthiopurine;

2-amino-9- 2- bis(2,2,2-trifluoroethyl)phosphonylmethoxy!ethyl!-6-p-methoxyphenylthiopurine;

2-amino-9- 2- bis(2,2,2-trifluoroethyl)phosphonylmethoxy!ethyl!-6-m-methoxyphenylthiopurine;

2-amino-9- 2- bis(2,2,2-trifluoroethyl)phosphonylmethoxy!ethyl!-6-o-methoxyphenylthiopurine;

2-amino-9- 2- bis(2,2,2-trifluoroethyl)phosphonylmethoxy!ethyl!-6-p-ethoxyphenylthiopurine;

2-amino-9- 2- bis(2,2,2-trifluoroethyl)phosphonylmethoxy!propyl!-6-phenylthiopurine;

2-amino-9- 2- bis(2,2,2-trifluoroethyl)phosphonylmethoxy!propyl!-6-p-methoxyphenylthiopurine;

2-amino-9- 2- (2,2,2-trifluoroethyl)phosphonylmethoxy!ethyl!-6-phenylthiopurine;

2-amino-9- 2- (2,2,2-trifluoroethyl)phosphonylmethoxy!ethyl!-6-p-methoxyphenylthiopurine;

2-amino-9- 2- phosphonylmethoxy!ethyl!-6-phenylthiopurine;

2-amino-9- 2- phosphonylmethoxy!ethyl!-6-p-methoxyphenylthiopurine;

2-amino-9- 2- bis(2,2,2-trifluoroethyl)phosphonylmethoxy!ethyl!-6-p-butoxyphenylthiopurine;

2-amino-9- 2- bis(2,2,2-trifluoroethyl)phosphonylmethoxy!ethyl!-6-p-propoxyphenylthiopurine;

2-amino-9- 2- bis(2,2,2-trifluoroethyl)phosphonylmethoxy!ethyl!-6-p-isopropoxyphenylthiopurine; and

2-amino-9- 2- bis(2,2,2-trifluoroethyl)phosphonylmethoxy!ethyl!-6-p-isobutoxyphenylthiopurine.

Other exemplary compounds satisfying the fourth condition include:

2-amino-9- 2- bis(2,2,2-trifluoroethyl)phosphonylmethoxy!ethyl!-6-m-ethoxyphenylthiopurine;

2-amino-9- 2- bis(2,2,2-trifluoroethyl)phosphonylmethoxy!ethyl!-6-o-ethoxyphenylthiopurine;

2-amino-9- 2- bis(2,2,2-trifluoroethyl)phosphonylmethoxy!ethyl!-6-m-butoxyphenylthiopurine;

2-amino-9- 2- bis(2,2,2-trifluoroethyl)phosphonylmethoxy!ethyl!-6-m-propoxyphenylthiopurine;

2-amino-9- 2- bis(2,2,2-trifluoroethyl)phosphonylmethoxy!ethyl!-6-m-isopropoxyphenylthiopurine;

2-amino-9- 2- bis(2,2,2-trifluoroethyl)phosphonylmethoxy!ethyl!-6-m-isobutoxyphenylthiopurine;

2-amino-9- 2- bis(2,2,2-trifluoroethyl)phosphonylmethoxy!ethyl!-6-o-butoxyphenylthiopurine

2-amino-9- 2- bis(2,2,2-trifluoroethyl)phosphonylmethoxy!ethyl!-6-o-propoxyphenylthiopurine;

2-amino-9- 2- bis(2,2,2-trifluoroethyl)phosphonylmethoxy!ethyl!-6-o-isopropoxyphenylthiopurine;

2-amino-9- 2- bis(2,2,2-trifluoroethyl)phosphonylmethoxy!ethyl!-6-o-isobutoxyphenylthiopurine;

2-amino-9- 2- bis(2,2,2-trifluoroethyl)phosphonylmethoxy!propyl!-6-m-methoxyphenylthiopurine;

2-amino-9- 2- bis(2,2,2-trifluoroethyl)phosphonylmethoxy!propyl!-6-o-methoxyphenylthiopurine;

2-amino-9- 2- bis(2,2,2-trifluoroethyl)phosphonylmethoxy!propyl!-6-p-ethoxyphenylthiopurine;

2-amino-9- 2- bis(2,2,2-trifluoroethyl)phosphonylmethoxy!propyl!-6-m-ethoxyphenylthiopurine;

2-amino-9- 2- bis(2,2,2-trifluoroethyl)phosphonylmethoxy!propyl!-6-o-ethoxyphenylthiopurine;

2-amino-9- 2- bis(2,2,2-trifluoroethyl)phosphonylmethoxy!propyl!-6-p-butoxyphenylthiopurine;

2-amino-9- 2- bis(2,2,2-trifluoroethyl)phosphonylmethoxy!propyl!-6-p-propoxyphenylthiopurine;

2-amino-9- 2- bis(2,2,2-trifluoroethyl)phosphonylmethoxy!propyl!-6-p-isopropoxyphenylthiopurine;

2-amino-9- 2- bis(2,2,2-trifluoroethyl)phosphonylmethoxy!propyl!-6-p-isobutoxyphenylthiopurine;

2-amino-9- 2- bis(2,2,2-trifluoroethyl)phosphonylmethoxy!propyl!-6-m-butoxyphenylthiopurine;

2-amino-9- 2- bis(2,2,2-trifluoroethyl)phosphonylmethoxy!propyl!-6-m-propoxyphenylthiopurine;

2-amino-9- 2- bis(2,2,2-trifluoroethyl)phosphonylmethoxy!propyl!-6-m-isopropoxyphenylthiopurine;

2-amino-9- 2- bis(2,2,2-trifluoroethyl)phosphonylmethoxy!propyl!-6-m-isobutoxyphenylthiopurine;

2-amino-9- 2- bis(2,2,2-trifluoroethyl)phosphonylmethoxy!propyl!-6-o-butoxyphenylthiopurine;

2-amino-9- 2- bis(2,2,2-trifluoroethyl)phosphonylmethoxy!propyl!-6-o-propoxyphenylthiopurine;

2-amino-9- 2- bis(2,2,2-trifluoroethyl)phosphonylmethoxy!propyl!-6-o-isopropoxyphenylthiopurine;

2-amino-9- 2- bis(2,2,2-trifluoroethyl)phosphonylmethoxy!propyl!-6-o-isobutoxyphenylthiopurine;

2-amino-9- 2- (2,2,2-trifluoroethyl)phosphonylmethoxy!ethyl!-6-m-methoxyphenylthiopurine;

2-amino-9- 2- (2,2,2-trifluoroethyl)phosphonylmethoxy!ethyl!-6-o-methoxyphenylthiopurine;

2-amino-9- 2- (2,2,2-trifluoroethyl)phosphonylmethoxy!ethyl!-6-p-ethoxyphenylthiopurine;

2-amino-9- 2- (2,2,2-trifluoroethyl)phosphonylmethoxy!ethyl!-6-m-ethoxyphenylthiopurine;

2-amino-9- 2- (2,2,2-trifluoroethyl)phosphonylmethoxy!ethyl!-6-o-ethoxyphenylthiopurine;

2-amino-9- 2- (2,2,2-trifluoroethyl)phosphonylmethoxy!ethyl!-6-p-butoxyphenylthiopurine;

2-amino-9- 2- (2,2,2-trifluoroethyl)phosphonylmethoxy!ethyl!-6-p-propoxyphenylthiopurine;

2-amino-9- 2- (2,2,2-trifluoroethyl)phosphonylmethoxy!ethyl!-6-p-isopropoxyphenylthiopurine;

2-amino-9- 2- (2,2,2-trifluoroethyl)phosphonylmethoxy!ethyl!-6-p-isobutoxyphenylthiopurine;

2-amino-9- 2- (2,2,2-trifluoroethyl)phosphonylmethoxy!ethyl!-6-m-butoxyphenylthiopurine;

2-amino-9- 2- (2,2,2-trifluoroethyl)phosphonylmethoxy!ethyl!-6-m-propoxyphenylthiopurine;

2-amino-9- 2- (2,2,2-trifluoroethyl)phosphonylmethoxy!ethyl!-6-m-isopropoxyphenylthiopurine;

2-amino-9- 2- (2,2,2-trifluoroethyl)phosphonylmethoxy!ethyl!-6-m-isobutoxyphenylthiopurine;

2-amino-9- 2- (2,2,2-trifluoroethyl)phosphonylmethoxy!ethyl!-6-o-butoxyphenylthiopurine;

2-amino-9- 2- (2,2,2-trifluoroethyl)phosphonylmethoxy!ethyl!-6-o-propoxyphenylthiopurine;

2-amino-9- 2- (2,2,2-trifluoroethyl)phosphonylmethoxy!ethyl!-6-o-isopropoxyphenylthiopurine;

2-amino-9- 2- (2,2,2-trifluoroethyl)phosphonylmethoxy!ethyl!-6-o-isobutoxyphenylthiopurine;

2-amino-9- 2- (2,2,2-trifluoroethyl)phosphonylmethoxy!propyl!-6-phenylthiopurine;

2-amino-9- 2- (2,2,2-trifluoroethyl)phosphonylmethoxy!propyl!-6-p-methoxyphenylthiopurine;

2-amino-9- 2- (2,2,2-trifluoroethyl)phosphonylmethoxy!propyl!-6-m-methoxyphenylthiopurine;

2-amino-9- 2- (2,2,2-trifluoroethyl)phosphonylmethoxy!propyl!-6-o-methoxyphenylthiopurine;

2-amino-9- 2- (2,2,2-trifluoroethyl)phosphonylmethoxy!propyl!-6-p-ethoxyphenylthiopurine;

2-amino-9- 2- (2,2,2-trifluoroethyl)phosphonylmethoxy!propyl!-6-m-ethoxyphenylthiopurine;

2-amino-9- 2- (2,2,2-trifluoroethyl)phosphonylmethoxy!propyl!-6-o-ethoxyphenylthiopurine;

2-amino-9- 2- (2,2,2-trifluoroethyl)phosphonylmethoxy!propyl!-6-p-butoxyphenylthiopurine;

2-amino-9- 2- (2,2,2-trifluoroethyl)phosphonylmethoxy!propyl!-6-p-propoxyphenylthiopurine;

2-amino-9- 2- (2,2,2-trifluoroethyl)phosphonylmethoxy!propyl!-6-p-isopropoxyphenylthiopurine;

2-amino-9- 2- (2,2,2-trifluoroethyl)phosphonylmethoxy!propyl!-6-p-isobutoxyphenylthiopurine;

2-amino-9- 2- (2,2,2-trifluoroethyl)phosphonylmethoxy!propyl!-6-m-butoxyphenylthiopurine;

2-amino-9- 2- (2,2,2-trifluoroethyl)phosphonylmethoxy!propyl!-6-m-propoxyphenylthiopurine;

2-amino-9- 2- (2,2,2-trifluoroethyl)phosphonylmethoxy!propyl!-6-m-isopropoxyphenylthiopurine;

2-amino-9- 2- (2,2,2-trifluoroethyl)phosphonylmethoxy!propyl!-6-m-isobutoxyphenylthiopurine;

2-amino-9- 2- (2,2,2-trifluoroethyl)phosphonylmethoxy!propyl!-6-o-butoxyphenylthiopurine;

2-amino-9- 2- (2,2,2-trifluoroethyl)phosphonylmethoxy!propyl!-6-o-propoxyphenylthiopurine;

2-amino-9- 2- (2,2,2-trifluoroethyl)phosphonylmethoxy!propyl!-6-o-isopropoxyphenylthiopurine;

2-amino-9- 2- (2,2,2-trifluoroethyl)phosphonylmethoxy!propyl!-6-o-isobutoxyphenylthiopurine;

2-amino-9- 2-phosphonylmethoxyethyl!-6-m-methoxyphenylthiopurine;

2-amino-9- 2-phosphonylmethoxyethyl!-6-o-methoxyphenylthiopurine;

2-amino-9- 2-phosphonylmethoxyethyl!-6-p-ethoxyphenylthiopurine;

2-amino-9- 2-phosphonylmethoxyethyl!-6-m-ethoxyphenylthiopurine;

2-amino-9- 2-phosphonylmethoxyethyl!-6-o-ethoxyphenylthiopurine;

2-amino-9- 2-phosphonylmethoxyethyl!-6-p-butoxyphenylthiopurine;

2-amino-9- 2-phosphonylmethoxyethyl!-6-p-propoxyphenylthiopurine;

2-amino-9- 2-phosphonylmethoxyethyl!-6-p-isopropoxyphenylthiopurine;

2-amino-9- 2-phosphonylmethoxyethyl!-6-p-isobutoxyphenylthiopurine;

2-amino-9- 2-phosphonylmethoxyethyl!-6-m-butoxyphenylthiopurine;

2-amino-9- 2-phosphonylmethoxyethyl!-6-m-propoxyphenylthiopurine;

2-amino-9- 2-phosphonylmethoxyethyl!-6-m-isopropoxyphenylthiopurine;

2-amino-9- 2-phosphonylmethoxyethyl!-6-m-isobutoxyphenylthiopurine;

2-amino-9- 2-phosphonylmethoxyethyl!-6-o-butoxyphenylthiopurine;

2-amino-9- 2-phosphonylmethoxyethyl!-6-o-propoxyphenylthiopurine;

2-amino-9- 2-phosphonylmethoxyethyl!-6-o-isopropoxyphenylthiopurine;

2-amino-9- 2-phosphonylmethoxyethyl!-6-o-isobutoxyphenylthiopurine;

2-amino-9- 2-phosphonylmethoxypropyl!-6-phenylthiopurine;

2-amino-9- 2-phosphonylmethoxypropyl!-6-p-methoxyphenylthiopurine;

2-amino-9- 2-phosphonylmethoxypropyl!-6-m-methoxyphenylthiopurine; 2-amino-9- 2-phosphonylmethoxypropyl!-6-o-methoxyphenylthiopurine;

2-amino-9- 2-phosphonylmethoxypropyl!-6-p-ethoxyphenylthiopurine;

2-amino-9- 2-phosphonylmethoxypropyl!-6-m-ethoxyphenylthiopurine;

2-amino-9- 2-phosphonylmethoxypropyl!-6-o-ethoxyphenylthiopurine;

2-amino-9- 2-phosphonylmethoxypropyl!-6-p-butoxyphenylthiopurine;

2-amino-9- 2-phosphonylmethoxypropyl!-6-p-propoxyphenylthiopurine;

2-amino-9- 2-phosphonylmethoxypropyl!-6-p-isopropoxyphenylthiopurine;

2-amino-9- 2-phosphonylmethoxypropyl!-6-p-isobutoxyphenylthiopurine;

2-amino-9- 2-phosphonylmethoxypropyl!-6-m-butoxyphenylthiopurine;

2-amino-9- 2-phosphonylmethoxypropyl!-6-m-propoxyphenylthiopurine;

2-amino-9- 2-phosphonylmethoxypropyl!-6-m-isopropoxyphenylthiopurine;

2-amino-9- 2-phosphonylmethoxypropyl!-6-m-isobutoxyphenylthiopurine;

2-amino-9- 2-phosphonylmethoxypropyl!-6-o-butoxyphenylthiopurine;

2-amino-9- 2-phosphonylmethoxypropyl!-6-o-propoxyphenylthiopurine;

2-amino-9- 2-phosphonylmethoxypropyl!-6-o-isopropoxyphenylthiopurine; and

2-amino-9- 2-phosphonylmethoxypropyl!-6-o-isobutoxyphenylthiopurine.

The fifth condition for preferred compounds includes that R¹ is hydrogen atom or a C₁ -C₄ alkoxy group; R² and R³ are 2,2,2-trifluoroethyl groups; and R⁴ is hydrogen atom or methyl group. Examples of the preferred compounds satisfying this condition include:

2-amino-9- 2- bis(2,2,2-trifluoroethyl)phosphonylmethoxy!ethyl!-6-phenylthiopurine;

2-amino-9- 2- bis(2,2,2-trifluoroethyl)phosphonylmethoxy!ethyl!-6-p-methoxyphenylthiopurine;

2-amino-9- 2- bis(2,2,2-trifluoroethyl)phosphonylmethoxy!ethyl!-6-m-methoxyphenylthiopurine;

2-amino-9- 2- bis(2,2,2-trifluoroethyl)phosphonylmethoxy!ethyl!-6-o-methoxyphenylthiopurine;

2-amino-9- 2- bis(2,2,2-trifluoroethyl)phosphonylmethoxy!ethyl!6-p-ethoxyphenylthiopurine;

2-amino-9- 2- bis(2,2,2-trifluoroethyl)phosphonylmethoxy!propyl!-6-phenylthiopurine;

2-amino-9- 2- bis(2,2,2-trifluoroethyl)phosphonylmethoxy!propyl!-6-p-methoxyphenylthiopurine;

2-amino-9- 2- bis(2,2,2-trifluoroethyl)phosphonylmethoxy!ethyl!-6-p-butoxyphenylthiopurine;

2-amino-9- 2- bis(2,2,2-trifluoroethyl)phosphonylmethoxy!ethyl!-6-p-propoxyphenylthiopurine;

2-amino-9- 2- bis(2,2,2-trifluoroethyl)phosphonylmethoxy!ethyl!-6-p-isopropoxyphenylthiopurine; and

2-amino-9- 2- bis(2,2,2-trifluoroethyl)phosphonylmethoxy!ethyl!-6-p-isobutoxyphenylthiopurine.

Other exemplary compounds satisfying the fifth condition include;

2-amino-9- 2- bis(2,2,2-trifluoroethyl)phosphonylmethoxy!ethyl!-6-m-ethoxyphenylthiopurine;

2-amino-9- 2- bis(2,2,2-trifluoroethyl)phosphonylmethoxy!ethyl!-6-o-ethoxyphenylthiopurine;

2-amino-9- 2- bis(2,2,2-trifluoroethyl)phosphonylmethoxy!ethyl!-6-m-butoxyphenylthiopurine;

2-amino-9- 2- bis(2,2,2-trifluoroethyl)phosphonylmethoxy!ethyl!-6-m-propoxyphenylthiopurine;

2-amino-9- 2- bis(2,2,2-trifluoroethyl)phosphonylmethoxy!ethyl!-6-m-isopropoxyphenylthiopurine;

2-amino-9- 2- bis(2,2,2-trifluoroethyl)phosphonylmethoxy!ethyl!-6-m-isobutoxyphenylthiopurine;

2-amino-9- 2- bis(2,2,2-trifluoroethyl)phosphonylmethoxy!ethyl!-6-o-butoxyphenylthiopurine;

2-amino-9- 2- bis(2,2,2-trifluoroethyl)phosphonylmethoxy!ethyl!-6-o-propoxyphenylthiopurine;

2-amino-9- 2- bis(2,2,2-trifluoroethyl)phosphonylmethoxy!ethyl!-6-o-isopropoxyphenylthiopurine;

2-amino-9- 2- bis(2,2,2-trifluoroethyl)phosphonylmethoxy!ethyl!-6-o-isobutoxyphenylthiopurine;

2-amino-9- 2- bis(2,2,2-trifluoroethyl)phosphonylmethoxy!propyl!-6-m-methoxyphenylthiopurine;

2-amino-9- 2- bis(2,2,2-trifluoroethyl)phosphonylmethoxy!propyl!-6-o-methoxyphenylthiopurine;

2-amino-9- 2- bis(2,2,2-trifluoroethyl)phosphonylmethoxy!propyl!-6-p-ethoxyphenylthiopurine;

2-amino-9- 2- bis(2,2,2-trifluoroethyl)phosphonylmethoxy!propyl!-6-m-ethoxyphenylthiopurine;

2-amino-9- 2- bis(2,2,2-trifluoroethyl)phosphonylmethoxy!propyl!-6-o-ethoxyphenylthiopurine;

2-amino-9- 2- bis(2,2,2-trifluoroethyl)phosphonylmethoxy!propyl!-6-p-butoxyphenylthiopurine;

2-amino-9- 2- bis(2,2,2-trifluoroethyl)phosphonylmethoxy!propyl!-6-p-propoxyphenylthiopurine;

2-amino-9- 2- bis(2,2,2-trifluoroethyl)phosphonylmethoxy!propyl!-6-p-isopropoxyphenylthiopurine;

2-amino-9- 2- bis(2,2,2-trifluoroethyl)phosphonylmethoxy!propyl!-6-p-isobutoxyphenylthiopurine;

2-amino-9- 2- bis(2,2,2-trifluoroethyl)phosphonylmethoxy!propyl!-6-m-butoxyphenylthiopurine;

2-amino-9- 2- bis(2,2,2-trifluoroethyl)phosphonylmethoxy!propyl!-6-m-propoxyphenylthiopurine;

2-amino-9- 2- bis(2,2,2-trifluoroethyl)phosphonylmethoxy!propyl!-6-m-isopropoxyphenylthiopurine;

2-amino-9- 2- bis(2,2,2-trifluoroethyl)phosphonylmethoxy!propyl!-6-m-isobutoxyphenylthiopurine;

2-amino-9- 2- bis(2,2,2-trifluoroethyl)phosphonylmethoxy!propyl!-6-o-butoxyphenylthiopurine;

2-amino-9- 2- bis(2,2,2-trifluoroethyl)phosphonylmethoxy!propyl!-6-o-propoxyphenylthiopurine;

2-amino-9- 2- bis(2,2,2-trifluoroethyl)phosphonylmethoxy!propyl!-6-o-isopropoxyphenylthiopurine; and

2-amino-9- 2- bis(2,2,2-trifluoroethyl)phosphonylmethoxy!propyl!-6-o-isobutoxyphenylthiopurine.

The sixth condition for preferred compounds includes that R¹ is hydrogen atom or a C¹ -C₄ alkoxy group; R² and R³ are 2,2,2-trifluoroethyl groups; and R⁴ is hydrogen atom. Examples of the preferred compounds satisfying this condition include:

2-amino-9- 2- bis(2,2,2-trifluoroethyl)phosphonylmethoxy!ethyl!-6-phenylthiopurine;

2-amino-9- 2- bis(2,2,2-trifluoroethyl)phosphonylmethoxy!ethyl!-6-p-methoxyphenylthiopurine;

2-amino-9- 2- bis(2,2,2-trifluoroethyl)phosphonylmethoxy!ethyl!-6-m-methoxyphenylthiopurine;

2-amino-9- 2- bis(2,2,2-trifluoroethyl)phosphonylmethoxy!ethyl!-6-o-methoxyphenylthiopurine;

2-amino-9- 2- bis(2,2,2-trifluoroethyl)phosphonylmethoxy!ethyl!-6-p-ethoxyphenylthiopurine;

2-amino-9- 2- bis(2,2,2-trifluoroethyl)phosphonylmethoxy!ethyl!-6-p-butoxyphenylthiopurine;

2-amino-9- 2- bis(2,2,2-trifluoroethyl)phosphonylmethoxy!ethyl!-6-p-propoxyphenylthiopurine;

2-amino-9- 2- bis(2,2,2-trifluoroethyl)phosphonylmethoxy!ethyl!-6-p-isopropoxyphenylthiopurine; and

2-amino-9- 2- bis(2,2,2-trifluoroethyl)phosphonylmethoxy!ethyl!-6-p-isobutoxyphenylthiopurine.

Other exemplary compounds satisfying the sixth condition include:

2-amino-9- 2- bis(2,2,2-trifluoroethyl)phosphonylmethoxy!ethyl!-6-m-ethoxyphenylthiopurine;

2-amino-9- 2- bis(2,2,2-trifluoroethyl)phosphonylmethoxy!ethyl!-6-o-ethoxyphenylthiopurine;

2-amino-9- 2- bis(2,2,2-trifluoroethyl)phosphonylmethoxy!ethyl!-6-m-butoxyphenylthiopurine;

2-amino-9- 2- bis(2,2,2-trifluoroethyl)phosphonylmethoxy!ethyl!-6-m-propoxyphenylthiopurine;

2-amino-9- 2- bis(2,2,2-trifluoroethyl)phosphonylmethoxy!ethyl!-6-m-isopropoxyphenylthiopurine;

2-amino-9- 2- bis(2,2,2-trifluoroethyl)phosphonylmethoxy!ethyl!-6-m-isobutoxyphenylthiopurine;

2-amino-9- 2- bis(2,2,2-trifluoroethyl)phosphonylmethoxy!ethyl!-6-o-butoxyphenylthiopurine;

2-amino-9- 2- bis(2,2,2-trifluoroethyl)phosphonylmethoxy!ethyl!-6-o-propoxyphenylthiopurine;

2-amino-9- 2- bis(2,2,2-trifluoroethyl)phosphonylmethoxy!ethyl!-6-o-isopropoxyphenylthiopurine; and

2-amino-9- 2- bis(2,2,2-trifluoroethyl)phosphonylmethoxy!ethyl!-6-o-isobutoxyphenylthiopurine.

The seventh condition for preferred compounds includes that R¹ is hydrogen atom or a C₁ -C₂ alkoxy group; R² and R³ are 2,2,2-trifluoroethyl groups, and R⁴ is hydrogen atom. Examples of the preferred compounds satisfying this condition include:

2-amino-9- 2- bis(2,2,2-trifluoroethyl)phosphonylmethoxy!ethyl!-6-phenylthiopurine;

2-amino-9- 2- bis(2,2,2-trifluoroethyl)phosphonylmethoxy!ethyl!-6-p-methoxyphenylthiopurine;

2-amino-9- 2- bis(2,2,2-trifluoroethyl)phosphonylmethoxy!ethyl!-6-m-methoxyphenylthiopurine;

2-amino-9- 2- bis(2,2,2-trifluoroethyl)phosphonylmethoxy!ethyl!-6-o-methoxyphenylthiopurine; and

2-amino-9- 2- bis(2,2,2-trifluoroethyl)phosphonylmethoxy!ethyl!-6-p-ethoxyphenylthiopurine.

Other exemplary compounds satisfying the seventh condition include:

2-amino-9- 2- bis(2,2,2-trifluoroethyl)phosphonylmethoxy!ethyl!-6-m-ethoxyphenylthiopurine; and

2-amino-9- 2- bis(2,2,2-trifluoroethyl)phosphonylmethoxy!ethyl!-6-o-ethoxyphenylthiopurine.

The phosphonate nucleotide compounds of the present invention represented by the above formula (I) may exist in the forms of salts, and any salts formed by the aforementioned compounds fall within the scope of the present invention. Examples of such salts include pharmaceutically acceptable salts. For example, where acidic groups exist, the acidic groups may form metal salts such as lithium salt, sodium salt, potassium salt, magnesium salt, or calcium salt, or ammonium salts such as ammonium salt, methylammonium salt, dimethylammonium salt, trimethylammonium salt, or dicyclohexylammonium salt. Where amino groups exist, they may form mineral acid salts such as hydrochloride, hydrobromide, sulfate, nitrate, phosphate, or metaphosphate, or organic acid salts such as methanesulfonate, benzenesulfonate, p-toluenesulfonate, acetate, propionate, tartarate, fumarate, maleate, malate, oxalate, succinate, citrate, benzoate, mandelate, cinnamate, lactate, besilate, valerate, stearate, oleate, lactobionate, ethylsuccinate, semisuccinate, butyrate, parmitate, carbamate, gluconate, laurate, salicylate, laoclate, tannate, or butylsulfonate.

The phosphonate nucleotide compounds of the present invention represented by the above general formula (I) and their salts may exist in the forms of hydrates or solvates. Any hydrates and solvates fall within the scope of the present invention which are formed by the phosphonate nucleotide compounds of the present invention represented by the above general formula (I) including the preferred compound specifically mentioned above. Examples of solvents which can form the solvate include methanol, ethanol, isopropanol, acetone, ethyl acetate, methylene chloride, or diisopropyl ether.

Specific examples of the compounds of the present invention will be listed in Table 1 set out below. In the table, symbols represent: Me-: methyl group; Et-: ethyl group; n-Pr-: normal-propyl group; i-Pr-: isopropyl group; n-Bu: normal-butyl group; i-Bu: isobutyl group; and t-Bu: tertiary-butyl group.

                                      TABLE 1                                      __________________________________________________________________________     No. R.sup.1                                                                             R.sup.2   R.sup.3   R.sup.4                                                                             X                                            __________________________________________________________________________       1 H    CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     H    C                                              2 o-OCH.sub.3                                                                         CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     H    C                                              3 m-OCH.sub.3                                                                         CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     H    C                                              4 p-OCH.sub.3                                                                         CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     H    C                                              5 o-Cl CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     H    C                                              6 m-Cl CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     H    C                                              7 p-Cl CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     H    C                                              8 o-Br CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     H    C                                              9 m-Br CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     H    C                                              10                                                                               p-Br CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     H    C                                              11                                                                               o-NH.sub.2                                                                          CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     H    C                                              12                                                                               m-NH.sub.2                                                                          CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     H    C                                              13                                                                               p-NH.sub.2                                                                          CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     H    C                                              14                                                                               o-NO.sub.2                                                                          CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     H    C                                              15                                                                               m-NO.sub.2                                                                          CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     H    C                                              16                                                                               p-NO.sub.2                                                                          CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     H    C                                              17                                                                               o-OC.sub.2 H.sub.5                                                                  CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     H    C                                              18                                                                               m-OC.sub.2 H.sub.5                                                                  CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     H    C                                              19                                                                               p-OC.sub.2 H.sub.5                                                                  CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     H    C                                              20                                                                               p-I  CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     H    C                                              21                                                                               o-O-n-Pr                                                                            CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     H    C                                              22                                                                               m-O-n-Pr                                                                            CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     H    C                                              23                                                                               p-O-n-Pr                                                                            CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     H    C                                              24                                                                               o-O-i-Pr                                                                            CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     H    C                                              25                                                                               m-O-i-Pr                                                                            CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     H    C                                              26                                                                               p-O-i-Pr                                                                            CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     H    C                                              27                                                                               o-O-n-Bu                                                                            CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     H    C                                              28                                                                               m-O-n-Bu                                                                            CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     H    C                                              29                                                                               p-O-n-Bu                                                                            CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     H    C                                              30                                                                               o-O-i-Bu                                                                            CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     H    C                                              31                                                                               m-O-i-Bu                                                                            CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     H    C                                              32                                                                               p-O-i-Bu                                                                            CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     H    C                                              33                                                                               o-OCF.sub.3                                                                         CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     H    C                                              34                                                                               m-OCF.sub.3                                                                         CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     H    C                                              35                                                                               p-OCF.sub.3                                                                         CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     H    C                                              36                                                                               H    CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     H    N                                              37                                                                               o-OCH.sub.3                                                                         CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     H    N                                              38                                                                               m-OCH.sub.3                                                                         CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     H    N                                              39                                                                               p-OCH.sub.3                                                                         CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     H    N                                              40                                                                               o-Cl CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     H    N                                              41                                                                               m-Cl CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     H    N                                              42                                                                               p-Cl CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     H    N                                              43                                                                               o-Br CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     H    N                                              44                                                                               m-Br CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     H    N                                              45                                                                               p-Br CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     H    N                                              46                                                                               o-NH.sub.2                                                                          CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     H    N                                              47                                                                               m-NH.sub.2                                                                          CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     H    N                                              48                                                                               p-NH.sub.2                                                                          CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     H    N                                              49                                                                               o-NO.sub.2                                                                          CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     H    N                                              50                                                                               m-NO.sub.2                                                                          CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     H    N                                              51                                                                               p-NO.sub.2                                                                          CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     H    N                                              52                                                                               o-OC.sub.2 H.sub.5                                                                  CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     H    N                                              53                                                                               m-OC.sub.2 H.sub.5                                                                  CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     H    N                                              54                                                                               p-OC.sub.2 H.sub.5                                                                  CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     H    N                                              55                                                                               p-I  CF.sub.3 CH.sub.3 -                                                                      CF.sub.3 CH.sub.2 --                                                                     H    N                                              56                                                                               o-O-n-Pr                                                                            CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     H    N                                              57                                                                               m-O-n-Pr                                                                            CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     H    N                                              58                                                                               p-O-n-Pr                                                                            CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     H    N                                              59                                                                               o-O-i-Pr                                                                            CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     H    N                                              60                                                                               m-O-i-Pr                                                                            CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     H                                                   61                                                                               p-O-i-Pr                                                                            CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     H    N                                              62                                                                               o-O-n-Bu                                                                            CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     H    N                                              63                                                                               m-O-n-Bu                                                                            CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     H    N                                              64                                                                               p-O-n-Bu                                                                            CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     H    N                                              65                                                                               o-O-i-Bu                                                                            CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     H    N                                              66                                                                               m-O-i-Bu                                                                            CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     H    N                                              67                                                                               p-O-i-Bu                                                                            CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     H    N                                              68                                                                               o-OCF.sub.3                                                                         CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     H    N                                              69                                                                               m-OCF.sub.3                                                                         CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     H    N                                              70                                                                               p-OCF.sub.3                                                                         CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     H    N                                              71                                                                               H    CF.sub.3 CH.sub.2 --                                                                     Me--      H    C                                              72                                                                               o-OCH.sub.3                                                                         CF.sub.3 CH.sub.2 --                                                                     Me--      H    C                                              73                                                                               m-OCH.sub.3                                                                         CF.sub.3 CH.sub.2 --                                                                     Me--      H    C                                              74                                                                               p-OCH.sub.3                                                                         CF.sub.3 CH.sub.2 --                                                                     Me--      H    C                                              75                                                                               o-Cl CF.sub.3 CH.sub.2 --                                                                     Me--      H    C                                              76                                                                               m-Cl CF.sub.3 CH.sub.2 --                                                                     Me--      H    C                                              77                                                                               p-Cl CF.sub.3 CH.sub.2 --                                                                     Me--      H    C                                              78                                                                               o-Br CF.sub.3 CH.sub.2 --                                                                     Me--      H    C                                              79                                                                               m-Br CF.sub.3 CH.sub.2 --                                                                     Me--      H    C                                              80                                                                               p-Br CF.sub.3 CH.sub.2 --                                                                     Me--      H    C                                              81                                                                               o-NH.sub.2                                                                          CF.sub.3 CH.sub.2 --                                                                     Me--      H    C                                              82                                                                               m-NH.sub.2                                                                          CF.sub.3 CH.sub.2 --                                                                     Me--      H    C                                              83                                                                               p-NH.sub.2                                                                          CF.sub.3 CH.sub.2 --                                                                     Me--      H    C                                              84                                                                               o-NO.sub.2                                                                          CF.sub.3 CH.sub.2 --                                                                     Me--      H    C                                              85                                                                               m-NO.sub.2                                                                          CF.sub.3 CH.sub.2 --                                                                     Me--      H    C                                              86                                                                               p-NO.sub.2                                                                          CF.sub.3 CH.sub.2 --                                                                     Me--      H    C                                              87                                                                               o-OC.sub.2 H.sub.5                                                                  CF.sub.3 CH.sub.2 --                                                                     Me--      H    C                                              88                                                                               m-OC.sub.2 H.sub.5                                                                  CF.sub.3 CH.sub.2 --                                                                     Me--      H    C                                              89                                                                               p-OC.sub.2 H.sub.5                                                                  CF.sub.3 CH.sub.2 --                                                                     Me--      H    C                                              90                                                                               p-I  CF.sub.3 CH.sub.2 --                                                                     Me--      H    C                                              91                                                                               o-O-n-Pr                                                                            CF.sub.3 CH.sub.2 --                                                                     Me--      H    C                                              92                                                                               m-O-n-Pr                                                                            CF.sub.3 CH.sub.2 --                                                                     Me--      H    C                                              93                                                                               p-O-n-Pr                                                                            CF.sub.3 CH.sub.2 --                                                                     Me--      H    C                                              94                                                                               o-O-i-Pr                                                                            CF.sub.3 CH.sub.2 --                                                                     Me--      H    C                                              95                                                                               m-O-i-Pr                                                                            CF.sub.3 CH.sub.2 --                                                                     Me--      H    C                                              96                                                                               p-O-i-Pr                                                                            CF.sub.3 CH.sub.2 --                                                                     Me--      H    C                                              97                                                                               o-O-n-Bu                                                                            CF.sub.3 CH.sub.2 --                                                                     Me--      H    C                                              98                                                                               m-O-n-Bu                                                                            CF.sub.3 CH.sub.2 --                                                                     Me--      H    C                                              99                                                                               p-O-n-Bu                                                                            CF.sub.3 CH.sub.2 --                                                                     Me--      H    C                                             100                                                                               o-O-i-Bu                                                                            CF.sub.3 CH.sub.2 --                                                                     Me--      H    C                                             101                                                                               m-O-i-Bu                                                                            CF.sub.3 CH.sub.2 --                                                                     Me--      H    C                                             102                                                                               p-O-i-Bu                                                                            CF.sub.3 CH.sub.2 --                                                                     Me--      H    C                                             103                                                                               o-OCF.sub.3                                                                         CF.sub.3 CH.sub.2 --                                                                     Me--      H    C                                             104                                                                               m-OCF.sub.3                                                                         CF.sub.3 CH.sub.2 --                                                                     Me--      H    C                                             105                                                                               p-OCF.sub.3                                                                         CF.sub.3 CH.sub.2 --                                                                     Me--      H    C                                             106                                                                               H    CF.sub.3 CH.sub.2 --                                                                     Me--      H    N                                             107                                                                               o-OCH.sub.3                                                                         CF.sub.3 CH.sub.2 --                                                                     Me--      H    N                                             108                                                                               m-OCH.sub.3                                                                         CF.sub.3 CH.sub.2 --                                                                     Me--      H    N                                             109                                                                               p-OCH.sub.3                                                                         CF.sub.3 CH.sub.2 --                                                                     Me--      H    N                                             110                                                                               o-Cl CF.sub.3 CH.sub.2 --                                                                     Me--      H    N                                             111                                                                               m-Cl CF.sub.3 CH.sub.2 --                                                                     Me--      H    N                                             112                                                                               p-Cl CF.sub.3 CH.sub.2 --                                                                     Me--      H    N                                             113                                                                               o-Br CF.sub.3 CH.sub.2 --                                                                     Me--      H    N                                             114                                                                               m-Br CF.sub.3 CH.sub.2 --                                                                     Me--      H    N                                             115                                                                               p-Br CF.sub.3 CH.sub.2 --                                                                     Me--      H    N                                             116                                                                               o-NH.sub.2                                                                          CF.sub.3 CH.sub.2 --                                                                     Me--      H    N                                             117                                                                               m-NH.sub.2                                                                          CF.sub.3 CH.sub.2 --                                                                     Me--      H    N                                             118                                                                               p-NH.sub.2                                                                          CF.sub.3 CH.sub.2 --                                                                     Me--      H    N                                             119                                                                               o-NO.sub.2                                                                          CF.sub.3 CH.sub.2 --                                                                     Me--      H    N                                             120                                                                               m-NO.sub.2                                                                          CF.sub.3 CH.sub.2 --                                                                     Me--      H    N                                             121                                                                               p-NO.sub.2                                                                          CF.sub.3 CH.sub.2 --                                                                     Me--      H    N                                             122                                                                               o-OC.sub.2 H.sub.5                                                                  CF.sub.3 CH.sub.2 --                                                                     Me--      H    N                                             123                                                                               m-OC.sub.2 H.sub.5                                                                  CF.sub.3 CH.sub.2 --                                                                     Me--      H    N                                             124                                                                               p-OC.sub.2 H.sub.5                                                                  CF.sub.3 CH.sub.2 --                                                                     Me--      H    N                                             125                                                                               p-I  CF.sub.3 CH.sub.2 --                                                                     Me--      H    N                                             126                                                                               o-O-n-Pr                                                                            CF.sub.3 CH.sub.2 --                                                                     Me--      H    N                                             127                                                                               m-O-n-Pr                                                                            CF.sub.3 CH.sub.2 --                                                                     Me--      H    N                                             128                                                                               p-O-n-Pr                                                                            CF.sub.3 CH.sub.2 --                                                                     Me--      H    N                                             129                                                                               o-O-i-Pr                                                                            CF.sub.3 CH.sub.2 --                                                                     Me--      H    N                                             130                                                                               m-O-i-Pr                                                                            CF.sub.3 CH.sub.2 --                                                                     Me--      H    N                                             131                                                                               p-O-i-Pr                                                                            CF.sub.3 CH.sub.2 --                                                                     Me--      H    N                                             132                                                                               o-O-n-Bu                                                                            CF.sub.3 CH.sub.2 --                                                                     Me--      H    N                                             133                                                                               m-O-n-Bu                                                                            CF.sub.3 CH.sub.2 --                                                                     Me--      H    N                                             134                                                                               p-O-n-Bu                                                                            CF.sub.3 CH.sub.2 --                                                                     Me--      H    N                                             135                                                                               o-O-i-Bu                                                                            CF.sub.3 CH.sub.2 --                                                                     Me--      H    N                                             136                                                                               m-O-i-Bu                                                                            CF.sub.3 CH.sub.2 --                                                                     Me--      H    N                                             137                                                                               p-O-i-Bu                                                                            CF.sub.3 CH.sub.2 --                                                                     Me--      H    N                                             138                                                                               o-OCF.sub.3                                                                         CF.sub.3 CH.sub.2 --                                                                     Me--      H    N                                             139                                                                               m-OCF.sub.3                                                                         CF.sub.3 CH.sub.2 --                                                                     Me--      H    N                                             140                                                                               p-OCF.sub.3                                                                         CF.sub.3 CH.sub.2 --                                                                     Me--      H    N                                             141                                                                               H    CF.sub.3 CH.sub.2 --                                                                     Et--      H    C                                             142                                                                               o-OCH.sub.3                                                                         CF.sub.3 CH.sub.2 --                                                                     Et--      H    C                                             143                                                                               m-OCH.sub.3                                                                         CF.sub.3 CH.sub.2 --                                                                     Et--      H    C                                             144                                                                               p-OCH.sub.3                                                                         CF.sub.3 CH.sub.2 --                                                                     Et--      H    C                                             145                                                                               o-Cl CF.sub.3 CH.sub.2 --                                                                     Et--      H    C                                             146                                                                               m-Cl CF.sub.3 CH.sub.2 --                                                                     Et--      H    C                                             147                                                                               p-Cl CF.sub.3 CH.sub.2 --                                                                     Et--      H    C                                             148                                                                               o-Br CF.sub.3 CH.sub.2 --                                                                     Et--      H    C                                             149                                                                               m-Br CF.sub.3 CH.sub.2 --                                                                     Et--      H    C                                             150                                                                               p-Br CF.sub.3 CH.sub.2 --                                                                     Et--      H    C                                             151                                                                               o-NH.sub.2                                                                          CF.sub.3 CH.sub.2 --                                                                     Et--      H    C                                             152                                                                               m-NH.sub.2                                                                          CF.sub.3 CH.sub.2 --                                                                     Et--      H    C                                             153                                                                               p-NH.sub.2                                                                          CF.sub.3 CH.sub.2 --                                                                     Et--      H    C                                             154                                                                               o-NO.sub.2                                                                          CF.sub.3 CH.sub.2 --                                                                     Et--      H    C                                             155                                                                               m-NO.sub.2                                                                          CF.sub.3 CH.sub.2 --                                                                     Et--      H    C                                             156                                                                               p-NO.sub.2                                                                          CF.sub.3 CH.sub.2 --                                                                     Et--      H    C                                             157                                                                               o-OC.sub.2 H.sub.5                                                                  CF.sub.3 CH.sub.2 --                                                                     Et--      H    C                                             158                                                                               m-OC.sub.2 H.sub.5                                                                  CF.sub.3 CH.sub.2 --                                                                     Et--      H    C                                             159                                                                               p-OC.sub.2 H.sub.5                                                                  CF.sub.3 CH.sub.2 --                                                                     Et--      H    C                                             160                                                                               p-I  CF.sub.3 CH.sub.2 --                                                                     Et--      H    C                                             161                                                                               o-O-n-Pr                                                                            CF.sub.3 CH.sub.2 --                                                                     Et--      H    C                                             162                                                                               m-O-n-Pr                                                                            CF.sub.3 CH.sub.2 --                                                                     Et--      H    C                                             163                                                                               p-O-n-Pr                                                                            CF.sub.3 CH.sub.2 --                                                                     Et--      H    C                                             164                                                                               o-O-i-Pr                                                                            CF.sub.3 CH.sub.2 --                                                                     Et--      H    C                                             165                                                                               m-O-i-Pr                                                                            CF.sub.3 CH.sub.2 --                                                                     Et--      H    C                                             166                                                                               p-O-i-Pr                                                                            CF.sub.3 CH.sub.2 --                                                                     Et--      H    C                                             167                                                                               o-O-n-Bu                                                                            CF.sub.3 CH.sub.2 --                                                                     Et--      H    C                                             168                                                                               m-O-n-Bu                                                                            CF.sub.3 CH.sub.2 --                                                                     Et--      H    C                                             169                                                                               p-O-n-Bu                                                                            CF.sub.3 CH.sub.2 --                                                                     Et--      H    C                                             170                                                                               o-O-i-Bu                                                                            CF.sub.3 CH.sub.2 --                                                                     Et--      H    C                                             171                                                                               m-O-i-BU                                                                            CF.sub.3 CH.sub.2 --                                                                     Et--      H    C                                             172                                                                               p-O-i-Bu                                                                            CF.sub.3 CH.sub.2 --                                                                     Et--      H    C                                             173                                                                               o-OCF.sub.3                                                                         CF.sub.3 CH.sub.2 --                                                                     Et--      H    C                                             174                                                                               m-OCF.sub.3                                                                         CF.sub.3 CH.sub.2 --                                                                     Et--      H    C                                             175                                                                               p-OCF.sub.3                                                                         CF.sub.3 CH.sub.2 --                                                                     Et--      H    C                                             176                                                                               H    CF.sub.3 CH.sub.2 --                                                                     Et--      H    N                                             177                                                                               o-OCH.sub.3                                                                         CF.sub.3 CH.sub.2 --                                                                     Et--      H    N                                             178                                                                               m-OCH.sub.3                                                                         CF.sub.3 CH.sub.2 --                                                                     Et--      H    N                                             179                                                                               p-OCH.sub.3                                                                         CF.sub.3 CH.sub.2 --                                                                     Et--      H    N                                             180                                                                               o-Cl CF.sub.3 CH.sub.2 --                                                                     Et--      H    N                                             181                                                                               m-Cl CF.sub.3 CH.sub.2 --                                                                     Et--      H    N                                             182                                                                               p-Cl CF.sub.3 CH.sub.2 --                                                                     Et--      H    N                                             183                                                                               o-Br CF.sub.3 CH.sub.2 --                                                                     Et--      H    N                                             184                                                                               m-Br CF.sub.3 CH.sub.2 --                                                                     Et--      H    N                                             185                                                                               p-Br CF.sub.3 CH.sub.2 --                                                                     Et--      H    N                                             186                                                                               o-NH.sub.2                                                                          CF.sub.3 CH.sub.2 --                                                                     Et--      H    N                                             187                                                                               m-NH.sub.2                                                                          CF.sub.3 CH.sub.2 --                                                                     Et--      H    N                                             188                                                                               p-NH.sub.2                                                                          CF.sub.3 CH.sub.2 --                                                                     Et--      H    N                                             189                                                                               o-NO.sub.2                                                                          CF.sub.3 CH.sub.2 --                                                                     Et--      H    N                                             190                                                                               m-NO.sub.2                                                                          CF.sub.3 CH.sub.2 --                                                                     Et--      H    N                                             191                                                                               p-NO.sub.2                                                                          CF.sub.3 CH.sub.2 --                                                                     Et--      H    N                                             192                                                                               o-OC.sub.2 H.sub.5                                                                  CF.sub.3 CH.sub.2 --                                                                     Et--      H    N                                             193                                                                               m-OC.sub.2 H.sub.5                                                                  CF.sub.3 CH.sub.2 --                                                                     Et--      H    N                                             194                                                                               p-OC.sub.2 H.sub.5                                                                  CF.sub.3 CH.sub.2 --                                                                     Et--      H    N                                             195                                                                               p-I  CF.sub.3 CH.sub.2 --                                                                     Et--      H    N                                             196                                                                               o-O-n-Pr                                                                            CF.sub.3 CH.sub.2 --                                                                     Et--      H    N                                             197                                                                               m-O-n-Pr                                                                            CF.sub.3 CH.sub.2 --                                                                     Et--      H    N                                             198                                                                               p-O-n-Pr                                                                            CF.sub.3 CH.sub.2 --                                                                     Et--      H    N                                             199                                                                               o-O-i-Pr                                                                            CF.sub.3 CH.sub.2 --                                                                     Et--      H    N                                             200                                                                               m-O-i-Pr                                                                            CF.sub.3 CH.sub.2 --                                                                     Et--      H    N                                             201                                                                               p-O-i-Pr                                                                            CF.sub.3 CH.sub.2 --                                                                     Et--      H    N                                             202                                                                               o-O-n-Bu                                                                            CF.sub.3 CH.sub.2 --                                                                     Et--      H    N                                             203                                                                               m-O-n-Bu                                                                            CF.sub.3 CH.sub.2 --                                                                     Et--      H    N                                             204                                                                               p-O-n-Bu                                                                            CF.sub.3 CH.sub.2 --                                                                     Et--      H    N                                             205                                                                               o-O-i-Bu                                                                            CF.sub.3 CH.sub.2 --                                                                     Et--      H    N                                             206                                                                               m-O-i-Bu                                                                            CF.sub.3 CH.sub.2 --                                                                     Et--      H    N                                             207                                                                               p-O-i-Bu                                                                            CF.sub.3 CH.sub.2 --                                                                     Et--      H    N                                             208                                                                               o-OCF.sub.3                                                                         CF.sub.3 CH.sub.2 --                                                                     Et--      H    N                                             209                                                                               m-OCF.sub.3                                                                         CF.sub.3 CH.sub.2 --                                                                     Et--      H    N                                             210                                                                               p-OCF.sub.3                                                                         CF.sub.3 CH.sub.2 --                                                                     Et--      H    N                                             211                                                                               H    CF.sub.3 CH.sub.2 --                                                                     H         H    C                                             212                                                                               o-OCH.sub.3                                                                         CF.sub.3 CH.sub.2 --                                                                     H         H    C                                             213                                                                               m-OCH.sub.3                                                                         CF.sub.3 CH.sub.2 --                                                                     H         H    C                                             214                                                                               p-OCH.sub.3                                                                         CF.sub.3 CH.sub.2 --                                                                     H         H    C                                             215                                                                               o-Cl CF.sub.3 CH.sub.2 --                                                                     H         H    C                                             216                                                                               m-Cl CF.sub.3 CH.sub.2 --                                                                     H         H    C                                             217                                                                               p-Cl CF.sub.3 CH.sub.2 --                                                                     H         H    C                                             218                                                                               o-Br CF.sub.3 CH.sub.2 --                                                                     H         H    C                                             219                                                                               m-Br CF.sub.3 CH.sub.2 --                                                                     H         H    C                                             220                                                                               p-Br CF.sub.3 CH.sub.2 --                                                                     H         H    C                                             221                                                                               o-NH.sub.2                                                                          CF.sub.3 CH.sub.2 --                                                                     H         H    C                                             222                                                                               m-NH.sub.2                                                                          CF.sub.3 CH.sub.2 --                                                                     H         H    C                                             223                                                                               p-NH.sub.2                                                                          CF.sub.3 CH.sub.2 --                                                                     H         H    C                                             224                                                                               o-NO.sub.2                                                                          CF.sub.3 CH.sub.2 --                                                                     H         H    C                                             225                                                                               m-NO.sub.2                                                                          CF.sub.3 CH.sub.2 --                                                                     H         H    C                                             226                                                                               p-NO.sub.2                                                                          CF.sub.3 CH.sub.2 --                                                                     H         H    C                                             227                                                                               o-OC.sub.2 H.sub.5                                                                  CF.sub.3 CH.sub.2 --                                                                     H         H    C                                             228                                                                               m-OC.sub.2 H.sub.5                                                                  CF.sub.3 CH.sub.2 --                                                                     H         H    C                                             229                                                                               p-OC.sub.2 H.sub.5                                                                  CF.sub.3 CH.sub.2 --                                                                     H         H    C                                             230                                                                               p-I  CF.sub.3 CH.sub.2 --                                                                     H         H    C                                             231                                                                               o-O-n-Pr                                                                            CF.sub.3 CH.sub.2 --                                                                     H         H    C                                             232                                                                               m-O-n-Pr                                                                            CF.sub.3 CH.sub.2 --                                                                     H         H    C                                             233                                                                               p-O-n-Pr                                                                            CF.sub.3 CH.sub.2 --                                                                     H         H    C                                             234                                                                               o-O-i-Pr                                                                            CF.sub.3 CH.sub.2 --                                                                     H         H    C                                             235                                                                               m-O-i-Pr                                                                            CF.sub.3 CH.sub.2 --                                                                     H         H    C                                             236                                                                               p-O-i-Pr                                                                            CF.sub.3 CH.sub.2 --                                                                     H         H    C                                             237                                                                               o-O-n-Bu                                                                            CF.sub.3 CH.sub.2 --                                                                     H         H    C                                             238                                                                               m-O-n-BU                                                                            CF.sub.3 CH.sub.2 --                                                                     H         H    C                                             239                                                                               p-O-n-Bu                                                                            CF.sub.3 CH.sub.2 --                                                                     H         H    C                                             240                                                                               o-O-i-Bu                                                                            CF.sub.3 CH.sub.2 --                                                                     H         H    C                                             241                                                                               m-O-i-Bu                                                                            CF.sub.3 CH.sub.2 --                                                                     H         H    C                                             242                                                                               p-O-i-Bu                                                                            CF.sub.3 CH.sub.2 --                                                                     H         H    C                                             243                                                                               o-OCF.sub.3                                                                         CF.sub.3 CH.sub.2 --                                                                     H         H    C                                             244                                                                               m-OCF.sub.3                                                                         CF.sub.3 CH.sub.2 --                                                                     H         H    C                                             245                                                                               p-OCF.sub.3                                                                         CF.sub.3 CH.sub.2 --                                                                     H         H    C                                             246                                                                               H    CF.sub.3 CH.sub.2 --                                                                     H         H    N                                             247                                                                               o-OCH.sub.3                                                                         CF.sub.3 CH.sub.2 --                                                                     H         H    N                                             248                                                                               m-OCH.sub.3                                                                         CF.sub.3 CH.sub.2 --                                                                     H         H    N                                             249                                                                               p-OCH.sub.3                                                                         CF.sub.3 CH.sub.2 --                                                                     H         H    N                                             250                                                                               o-Cl CF.sub.3 CH.sub.2 --                                                                     H         H    N                                             251                                                                               m-Cl CF.sub.3 CH.sub.2 --                                                                     H         H    N                                             252                                                                               p-Cl CF.sub.3 CH.sub.2 --                                                                     H         H    N                                             253                                                                               o-Br CF.sub.3 CH.sub.2 --                                                                     H         H    N                                             254                                                                               m-Br CF.sub.3 CH.sub.2 --                                                                     H         H    N                                             255                                                                               p-Br CF.sub.3 CH.sub.2 --                                                                     H         H    N                                             256                                                                               o-NH.sub.2                                                                          CF.sub.3 CH.sub.2 --                                                                     H         H    N                                             257                                                                               m-NH.sub.2                                                                          CF.sub.3 CH.sub.2 --                                                                     H         H    N                                             258                                                                               p-NH.sub.2                                                                          CF.sub.3 CH.sub.2 --                                                                     H         H    N                                             259                                                                               o-NO.sub.2                                                                          CF.sub.3 CH.sub.2 --                                                                     H         H    N                                             260                                                                               m-NO.sub.2                                                                          CF.sub.3 CH.sub.2 --                                                                     H         H    N                                             261                                                                               p-NO.sub.2                                                                          CF.sub.3 CH.sub.2 --                                                                     H         H    N                                             262                                                                               o-OC.sub.2 H.sub.5                                                                  CF.sub.3 CH.sub.2 --                                                                     H         H    N                                             263                                                                               m-OC.sub.2 H.sub.5                                                                  CF.sub.3 CH.sub.2 --                                                                     H         H    N                                             264                                                                               p-OC.sub.2 H.sub.5                                                                  CF.sub.3 CH.sub.2 --                                                                     H         H    N                                             265                                                                               p-I  CF.sub.3 CH.sub.2 --                                                                     H         H    N                                             266                                                                               o-O-n-Pr                                                                            CF.sub.3 CH.sub.2 --                                                                     H         H    N                                             267                                                                               m-O-n-Pr                                                                            CF.sub.3 CH.sub.2 --                                                                     H         H    N                                             268                                                                               p-O-n-Pr                                                                            CF.sub.3 CH.sub.2 --                                                                     H         H    N                                             269                                                                               o-O-i-Pr                                                                            CF.sub.3 CH.sub.2 --                                                                     H         H    N                                             270                                                                               m-O-i-Pr                                                                            CF.sub.3 CH.sub.2 --                                                                     H         H    N                                             271                                                                               p-O-i-Pr                                                                            CF.sub.3 CH.sub.2 --                                                                     H         H    N                                             272                                                                               o-O-n-Bu                                                                            CF.sub.3 CH.sub.2 --                                                                     H         H    N                                             273                                                                               m-O-n-Bu                                                                            CF.sub.3 CH.sub.2 --                                                                     H         H    N                                             274                                                                               p-O-n-Bu                                                                            CF.sub.3 CH.sub.2 --                                                                     H         H    N                                             275                                                                               o-O-i-Bu                                                                            CF.sub.3 CH.sub.2 --                                                                     H         H    N                                             276                                                                               m-O-i-Bu                                                                            CF.sub.3 CH.sub.2 --                                                                     H         H    N                                             277                                                                               p-O-i-Bu                                                                            CF.sub.3 CH.sub.2 --                                                                     H         H    N                                             278                                                                               o-OCF.sub.3                                                                         CF.sub.3 CH.sub.2 --                                                                     H         H    N                                             279                                                                               m-OCF.sub.3                                                                         CF.sub.3 CH.sub.2 --                                                                     H         H    N                                             280                                                                               p-OCF.sub.3                                                                         CF.sub.3 CH.sub.2 --                                                                     H         H    N                                             281                                                                               H    H         H         H    C                                             282                                                                               o-OCH.sub.3                                                                         H         H         H    C                                             283                                                                               m-OCH.sub.3                                                                         H         H         H    C                                             284                                                                               p-OCH.sub.3                                                                         H         H         H    C                                             285                                                                               o-Cl H         H         H    C                                             286                                                                               m-Cl H         H         H    C                                             287                                                                               p-Cl H         H         H    C                                             288                                                                               o-Br H         H         H    C                                             289                                                                               m-Br H         H         H    C                                             290                                                                               p-Br H         H         H    C                                             291                                                                               o-NH.sub.2                                                                          H         H         H    C                                             292                                                                               m-NH.sub.2                                                                          H         H         H    C                                             293                                                                               p-NH.sub.2                                                                          H         H         H    C                                             294                                                                               o-NO.sub.2                                                                          H         H         H    C                                             295                                                                               m-NO.sub.2                                                                          H         H         H    C                                             296                                                                               p-NO.sub.2                                                                          H         H         H    C                                             297                                                                               o-OC.sub.2 H.sub.5                                                                  H         H         H    C                                             298                                                                               m-OC.sub.2 H.sub.5                                                                  H         H         H    C                                             299                                                                               p-OC.sub.2 H.sub.5                                                                  H         H         H    C                                             300                                                                               p-I  H         H         H    C                                             301                                                                               o-O-n-Pr                                                                            H         H         H    C                                             302                                                                               m-O-n-Pr                                                                            H         H         H    C                                             303                                                                               p-O-n-Pr                                                                            H         H         H    C                                             304                                                                               o-O-i-Pr                                                                            H         H         H    C                                             305                                                                               m-O-i-Pr                                                                            H         H         H    C                                             306                                                                               p-O-i-Pr                                                                            H         H         H    C                                             307                                                                               o-O-n-Bu                                                                            H         H         H    C                                             308                                                                               m-O-n-Bu                                                                            H         H         H    C                                             309                                                                               p-O-n-Bu                                                                            H         H         H    C                                             310                                                                               o-O-i-Bu                                                                            H         H         H    C                                             311                                                                               m-O-i-Bu                                                                            H         H         H    C                                             312                                                                               p-o-i-Bu                                                                            H         H         H    C                                             313                                                                               o-OCF.sub.3                                                                         H         H         H    C                                             314                                                                               m-OCF.sub.3                                                                         H         H         H    C                                             315                                                                               p-OCF.sub.3                                                                         H         H         H    C                                             316                                                                               H    H         H         H    N                                             317                                                                               o-OCH.sub.3                                                                         H         H         H    N                                             318                                                                               m-OCH.sub.3                                                                         H         H         H    N                                             319                                                                               p-OCH.sub.3                                                                         H         H         H    N                                             320                                                                               o-Cl H         H         H    N                                             321                                                                               m-Cl H         H         H    N                                             322                                                                               p-Cl H         H         H    N                                             323                                                                               o-Br H         H         H    N                                             324                                                                               m-Br H         H         H    N                                             325                                                                               p-Br H         H         H    N                                             326                                                                               o-NH.sub.2                                                                          H         H         H    N                                             327                                                                               m-NH.sub.2                                                                          H         H         H    N                                             328                                                                               p-NH.sub.2                                                                          H         H         H    N                                             329                                                                               o-NO.sub.2                                                                          H         H         H    N                                             330                                                                               m-NO.sub.2                                                                          H         H         H    N                                             331                                                                               p-NO.sub.2                                                                          H         H         H    N                                             332                                                                               o-OC.sub.2 H.sub.5                                                                  H         H         H    N                                             333                                                                               m-OC.sub.2 H.sub.5                                                                  H         H         H    N                                             334                                                                               p-OC.sub.2 H.sub.5                                                                  H         H         H    N                                             335                                                                               p-I  H         H         H    N                                             336                                                                               o-O-n-Pr                                                                            H         H         H    N                                             337                                                                               m-O-n-Pr                                                                            H         H         H    N                                             338                                                                               p-O-n-Pr                                                                            H         H         H    N                                             339                                                                               o-O-i-Pr                                                                            H         H         H    N                                             340                                                                               m-O-i-Pr                                                                            H         H         H    N                                             341                                                                               p-O-i-Pr                                                                            H         H         H    N                                             342                                                                               o-O-n-Bu                                                                            H         H         H    N                                             343                                                                               m-O-n-Bu                                                                            H         H         H    N                                             344                                                                               p-O-n-Bu                                                                            H         H         H    N                                             345                                                                               o-O-i-Bu                                                                            H         H         H    N                                             346                                                                               m-O-i-Bu                                                                            H         H         H    N                                             347                                                                               p-O-i-Bu                                                                            H         H         H    N                                             348                                                                               o-OCF.sub.3                                                                         H         H         H    N                                             349                                                                               m-OCF.sub.3                                                                         H         H         H    N                                             350                                                                               p-OCF.sub.3                                                                         H         H         H    N                                             351                                                                               H    CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     Me-- C                                             352                                                                               o-OCH.sub.3                                                                         CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     Me-- C                                             353                                                                               m-OCH.sub.3                                                                         CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     Me-- C                                             354                                                                               p-OCH.sub.3                                                                         CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     Me-- C                                             355                                                                               o-Cl CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     Me-- C                                             356                                                                               m-Cl CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     Me-- C                                             357                                                                               p-Cl CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     Me-- C                                             358                                                                               o-Br CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     Me-- C                                             359                                                                               m-Br CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     Me-- C                                             360                                                                               p-Br CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     Me-- C                                             361                                                                               o-NH.sub.2                                                                          CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     Me-- C                                             362                                                                               m-NH.sub.2                                                                          CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     Me-- C                                             363                                                                               p-NH.sub.2                                                                          CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     Me-- C                                             364                                                                               o-NO.sub.2                                                                          CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     Me-- C                                             365                                                                               m-NO.sub.2                                                                          CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     Me-- C                                             366                                                                               p-NO.sub.2                                                                          CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     Me-- C                                             367                                                                               O-OC.sub.2 H.sub.5                                                                  CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     Me-- C                                             368                                                                               m-OC.sub.2 H.sub.5                                                                  CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     Me-- C                                             369                                                                               p-OC.sub.2 H.sub.5                                                                  CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     Me-- C                                             370                                                                               p-I  CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     Me-- C                                             371                                                                               o-O-n-Pr                                                                            CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     Me-- C                                             372                                                                               m-O-n-Pr                                                                            CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     Me-- C                                             373                                                                               p-O-n-Pr                                                                            CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     Me-- C                                             374                                                                               o-O-i-Pr                                                                            CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     Me-- C                                             375                                                                               m-O-i-Pr                                                                            CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     Me-- C                                             376                                                                               p-O-i-Pr                                                                            CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     Me-- C                                             377                                                                               o-O-n-Bu                                                                            CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     Me-- C                                             378                                                                               m-O-n-Bu                                                                            CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     Me-- C                                             379                                                                               p-O-n-Bu                                                                            CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     Me-- C                                             380                                                                               o-O-i-Bu                                                                            CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     Me-- C                                             381                                                                               m-O-i-Bu                                                                            CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     Me-- C                                             382                                                                               p-O-i-Bu                                                                            CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     Me-- C                                             383                                                                               o-OCF.sub.3                                                                         CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     Me-- C                                             384                                                                               m-OCF.sub.3                                                                         CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     Me-- C                                             385                                                                               p-OCF.sub.3                                                                         CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     Me-- C                                             386                                                                               H    CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     Me-- N                                             387                                                                               o-OCH.sub.3                                                                         CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     Me-- N                                             388                                                                               m-OCH.sub.3                                                                         CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     Me-- N                                             389                                                                               p-OCH.sub.3                                                                         CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     Me-- N                                             390                                                                               o-Cl CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     Me-- N                                             391                                                                               m-Cl CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     Me-- N                                             392                                                                               p-Cl CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     Me-- N                                             393                                                                               o-Br CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     Me-- N                                             394                                                                               m-Br CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     Me-- N                                             395                                                                               p-Br CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     Me-- N                                             396                                                                               o-NH.sub.2                                                                          CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     Me-- N                                             397                                                                               m-NH.sub.2                                                                          CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     Me-- N                                             398                                                                               p-NH.sub.2                                                                          CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     Me-- N                                             399                                                                               o-NO.sub.2                                                                          CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     Me-- N                                             400                                                                               m-NO.sub.2                                                                          CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     Me-- N                                             401                                                                               p-NO.sub.2                                                                          CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     Me-- N                                             402                                                                               o-OC.sub.2 H.sub.5                                                                  CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     Me-- N                                             403                                                                               m-OC.sub.2 H.sub.5                                                                  CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     Me-- N                                             404                                                                               p-OC.sub.2 H.sub.5                                                                  CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     Me-- N                                             405                                                                               p-I  CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     Me-- N                                             406                                                                               o-O-n-Pr                                                                            CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     Me-- N                                             407                                                                               m-O-n-Pr                                                                            CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     Me-- N                                             408                                                                               p-O-n-Pr                                                                            CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     Me-- N                                             409                                                                               o-O-i-Pr                                                                            CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     Me-- N                                             410                                                                               m-O-i-Pr                                                                            CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     Me-- N                                             411                                                                               p-O-i-Pr                                                                            CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     Me-- N                                             412                                                                               o-O-n-Bu                                                                            CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     Me-- N                                             413                                                                               m-O-n-Bu                                                                            CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     Me-- N                                             414                                                                               p-O-n-Bu                                                                            CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     Me-- N                                             415                                                                               o-O-i-Eu                                                                            CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     Me-- N                                             416                                                                               m-O-i-Bu                                                                            CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     Me-- N                                             417                                                                               p-O-i-Bu                                                                            CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     Me-- N                                             418                                                                               o-OCF.sub.3                                                                         CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     Me-- N                                             419                                                                               m-OCF.sub.3                                                                         CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     Me-- N                                             420                                                                               p-OCF.sub.3                                                                         CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     Me-- N                                             421                                                                               H    CF.sub.3 CH.sub.2 --                                                                     Me--      Me-- C                                             422                                                                               o-OCH.sub.3                                                                         CF.sub.3 CH.sub.2 --                                                                     Me--      Me-- C                                             423                                                                               m-OCH.sub.3                                                                         CF.sub.3 CH.sub.2 --                                                                     Me--      Me-- C                                             424                                                                               p-OCH.sub.3                                                                         CF.sub.3 CH.sub.2 --                                                                     Me--      Me-- C                                             425                                                                               o-Cl CF.sub.3 CH.sub.2 --                                                                     Me--      Me-- C                                             426                                                                               m-Cl CF.sub.3 CH.sub.2 --                                                                     Me--      Me-- C                                             427                                                                               p-Cl CF.sub.3 CH.sub.2 --                                                                     Me--      Me-- C                                             428                                                                               o-Br CF.sub.3 CH.sub.2 --                                                                     Me--      Me-- C                                             429                                                                               m-Br CF.sub.3 CH.sub.2 --                                                                     Me--      Me-- C                                             430                                                                               p-Br CF.sub.3 CH.sub.2 --                                                                     Me--      Me-- C                                             431                                                                               o-NH.sub.2                                                                          CF.sub.3 CH.sub.2 --                                                                     Me--      Me-- C                                             432                                                                               m-NH.sub.2                                                                          CF.sub.3 CH.sub.2 --                                                                     Me--      Me-- C                                             433                                                                               p-NH.sub.2                                                                          CF.sub.3 CH.sub.2 --                                                                     Me--      Me-- C                                             434                                                                               o-NO.sub.2                                                                          CF.sub.3 CH.sub.2 --                                                                     Me--      Me-- C                                             435                                                                               m-NO.sub.2                                                                          CF.sub.3 CH.sub.2 --                                                                     Me--      Me-- C                                             436                                                                               p-NO.sub.2                                                                          CF.sub.3 CH.sub.2 --                                                                     Me--      Me-- C                                             437                                                                               o-OC.sub.2 H.sub.5                                                                  CF.sub.3 CH.sub.2 --                                                                     Me--      Me-- C                                             438                                                                               m-OC.sub.2 H.sub.5                                                                  CF.sub.3 CH.sub.2 --                                                                     Me--      Me-- C                                             439                                                                               p-OC.sub.2 H.sub.5                                                                  CF.sub.3 CH.sub.2 --                                                                     Me--      Me-- C                                             440                                                                               p-I  CF.sub.3 CH.sub.2 --                                                                     Me--      Me-- C                                             441                                                                               o-O-n-Pr                                                                            CF.sub.3 CH.sub.2 --                                                                     Me--      Me-- C                                             442                                                                               m-O-n-Pr                                                                            CF.sub.3 CH.sub.2 --                                                                     Me--      Me-- C                                             443                                                                               p-O-n-Pr                                                                            CF.sub.3 CH.sub.2 --                                                                     Me--      Me-- C                                             444                                                                               o-O-i-Pr                                                                            CF.sub.3 CH.sub.2 --                                                                     Me--      Me-- C                                             445                                                                               m-O-i-Pr                                                                            CF.sub.3 CH.sub.2 --                                                                     Me--      Me-- C                                             446                                                                               p-O-i-Pr                                                                            CF.sub.3 CH.sub.2 --                                                                     Me--      Me-- C                                             447                                                                               o-O-n-Bu                                                                            CF.sub.3 CH.sub.2 --                                                                     Me--      Me-- C                                             448                                                                               m-O-n-Bu                                                                            CF.sub.3 CH.sub.2 --                                                                     Me--      Me-- C                                             449                                                                               p-O-n-Bu                                                                            CF.sub.3 CH.sub.2 --                                                                     Me--      Me-- C                                             450                                                                               o-O-i-Bu                                                                            CF.sub.3 CH.sub.2 --                                                                     Me--      Me-- C                                             451                                                                               m-O-i-Bu                                                                            CF.sub.3 CH.sub.2 --                                                                     Me--      Me-- C                                             452                                                                               p-O-i-Bu                                                                            CF.sub.3 CH.sub.2 --                                                                     Me--      Me-- C                                             453                                                                               o-OCF.sub.3                                                                         CF.sub.3 CH.sub.2 --                                                                     Me--      Me-- C                                             454                                                                               m-OCF.sub.3                                                                         CF.sub.3 CH.sub.2 --                                                                     Me--      Me-- C                                             455                                                                               p-OCF.sub.3                                                                         CF.sub.3 CH.sub.2 --                                                                     Me--      Me-- C                                             456                                                                               H    CF.sub.3 CH.sub.2 --                                                                     Me--      Me-- N                                             457                                                                               o-OCH.sub.3                                                                         CF.sub.3 CH.sub.2 --                                                                     Me--      Me-- N                                             458                                                                               m-OCH.sub.3                                                                         CF.sub.3 CH.sub.2 --                                                                     Me--      Me-- N                                             459                                                                               p-OCH.sub.3                                                                         CF.sub.3 CH.sub.2 --                                                                     Me--      Me-- N                                             460                                                                               o-Cl CF.sub.3 CH.sub.2 --                                                                     Me--      Me-- N                                             461                                                                               m-Cl CF.sub.3 CH.sub.2 --                                                                     Me--      Me-- N                                             462                                                                               p-Cl CF.sub.3 CH.sub.2 --                                                                     Me--      Me-- N                                             463                                                                               o-Br CF.sub.3 CH.sub.2 --                                                                     Me--      Me-- N                                             464                                                                               m-Br CF.sub.3 CH.sub.2 --                                                                     Me--      Me-- N                                             465                                                                               p-Br CF.sub.3 CH.sub.2 --                                                                     Me--      Me-- N                                             466                                                                               o-NH.sub.2                                                                          CF.sub.3 CH.sub.2 --                                                                     Me--      Me-- N                                             467                                                                               m-NH.sub.2                                                                          CF.sub.3 CH.sub.2 --                                                                     Me--      Me-- N                                             468                                                                               p-NH.sub.2                                                                          CF.sub.3 CH.sub.2 --                                                                     Me--      Me-- N                                             469                                                                               o-NO.sub.2                                                                          CF.sub.3 CH.sub.2 --                                                                     Me--      Me-- N                                             470                                                                               m-NO.sub.2                                                                          CF.sub.3 CH.sub.2 --                                                                     Me--      Me-- N                                             471                                                                               p-NO3                                                                               CF.sub.3 CH.sub.2 --                                                                     Me--      Me-- N                                             472                                                                               o-OC3H5                                                                             CF.sub.3 CH.sub.2 --                                                                     Me--      Me-- N                                             473                                                                               m-OC.sub.2 H.sub.5                                                                  CF.sub.3 CH.sub.2 --                                                                     Me--      Me-- N                                             474                                                                               p-OC.sub.2 H.sub.5                                                                  CF.sub.3 CH.sub.2 --                                                                     Me--      Me-- N                                             475                                                                               p-I  CF.sub.3 CH.sub.2 --                                                                     Me--      Me-- N                                             476                                                                               o-O-n-Pr                                                                            CF.sub.3 CH.sub.2 --                                                                     Me--      Me-- N                                             477                                                                               m-O-n-Pr                                                                            CF.sub.3 CH.sub.3 -                                                                      Me--      Me-- N                                             478                                                                               p-O-n-Pr                                                                            CF.sub.3 CH.sub.2 --                                                                     Me--      Me-- N                                             479                                                                               o-O-i-Pr                                                                            CF.sub.3 CH.sub.2 --                                                                     Me--      Me-- N                                             480                                                                               m-O-i-Pr                                                                            CF.sub.3 CH.sub.2 --                                                                     Me--      Me-- N                                             481                                                                               p-O-i-Pr                                                                            CF.sub.3 CH.sub.2 --                                                                     Me--      Me-- N                                             482                                                                               o-O-n-Bu                                                                            CF.sub.3 CH.sub.2 --                                                                     Me--      Me-- N                                             483                                                                               m-O-n-Bu                                                                            CF.sub.3 CH.sub.2 --                                                                     Me--      Me-- N                                             484                                                                               p-O-n-Bu                                                                            CF.sub.3 CH.sub.2 --                                                                     Me--      Me-- N                                             485                                                                               o-O-i-Bu                                                                            CF.sub.3 CH.sub.2 --                                                                     Me--      Me-- N                                             486                                                                               m-O-i-Bu                                                                            CF.sub.3 CH.sub.2 --                                                                     Me--      Me-- N                                             487                                                                               p-O-i-Bu                                                                            CF.sub.3 CH.sub.2 --                                                                     Me--      Me-- N                                             488                                                                               o-OCF.sub.3                                                                         CF.sub.3 CH.sub.2 --                                                                     Me--      Me-- N                                             489                                                                               m-OCF.sub.3                                                                         CF.sub.3 CH.sub.2 --                                                                     Me--      Me-- N                                             490                                                                               p-OCF.sub.3                                                                         CF.sub.3 CH.sub.2 --                                                                     Me--      Me-- N                                             491                                                                               H    CF.sub.3 CH.sub.2 --                                                                     Et--      Me-- C                                             492                                                                               o-OCH.sub.3                                                                         CF.sub.3 CH.sub.2 --                                                                     Et--      Me-- C                                             493                                                                               m-OCH.sub.3                                                                         CF.sub.3 CH.sub.2 --                                                                     Et--      Me-- C                                             494                                                                               p-OCH.sub.3                                                                         CF.sub.3 CH.sub.2 --                                                                     Et--      Me-- C                                             495                                                                               o-Cl CF.sub.3 CH.sub.2 --                                                                     Et--      Me-- C                                             496                                                                               m-Cl CF.sub.3 CH.sub.2 --                                                                     Et--      Me-- C                                             497                                                                               p-Cl CF.sub.3 CH.sub.2 --                                                                     Et--      Me-- C                                             498                                                                               o-Br CF.sub.3 CH.sub.2 --                                                                     Et--      Me-- C                                             499                                                                               m-Br CF.sub.3 CH.sub.2 --                                                                     Et--      Me-- C                                             500                                                                               p-Br CF.sub.3 CH.sub.2 --                                                                     Et--      Me-- C                                             501                                                                               o-NH.sub.2                                                                          CF.sub.3 CH.sub.2 --                                                                     Et--      Me-- C                                             502                                                                               m-NH.sub.2                                                                          CF.sub.3 CH.sub.2 --                                                                     Et--      Me-- C                                             503                                                                               p-NH.sub.2                                                                          CF.sub.3 CH.sub.2 --                                                                     Et--      Me-- C                                             504                                                                               o-NO.sub.2                                                                          CF.sub.3 CH.sub.2 --                                                                     Et--      Me-- C                                             505                                                                               m-NO.sub.2                                                                          CF.sub.3 CH.sub.2 --                                                                     Et--      Me-- C                                             506                                                                               p-NO.sub.2                                                                          CF.sub.3 CH.sub.2 --                                                                     Et--      Me-- C                                             507                                                                               o-OC.sub.2 H.sub.5                                                                  CF.sub.3 CH.sub.2 --                                                                     Et--      Me-- C                                             508                                                                               m-OC.sub.2 H.sub.5                                                                  CF.sub.3 CH.sub.2 --                                                                     Et--      Me-- C                                             509                                                                               p-OC.sub.2 H.sub.5                                                                  CF.sub.3 CH.sub.2 --                                                                     Et--      Me-- C                                             510                                                                               p-I  CF.sub.3 CH.sub.2 --                                                                     Et--      Me--                                               511                                                                               o-O-n-Pr                                                                            CF.sub.3 CH.sub.2 --                                                                     Et--      Me-- C                                             512                                                                               m-O-n-Pr                                                                            CF.sub.3 CH.sub.2 --                                                                     Et--      Me-- C                                             513                                                                               p-O-n-Pr                                                                            CF.sub.3 CH.sub.2 --                                                                     Et--      Me-- C                                             514                                                                               o-O-i-Pr                                                                            CF.sub.3 CH.sub.2 --                                                                     Et--      Me-- C                                             515                                                                               m-O-i-Pr                                                                            CF.sub.3 CH.sub.2 --                                                                     Et--      Me-- C                                             516                                                                               p-O-i-Pr                                                                            CF.sub.3 CH.sub.2 --                                                                     Et--      Me-- C                                             517                                                                               o-O-n-Bu                                                                            CF.sub.3 CH.sub.2 --                                                                     Et--      Me-- C                                             518                                                                               m-O-n-Bu                                                                            CF.sub.3 CH.sub.2 --                                                                     Et--      Me-- C                                             519                                                                               p-O-n-Bu                                                                            CF.sub.3 CH.sub.2 --                                                                     Et--      Me-- C                                             520                                                                               o-O-i-Bu                                                                            CF.sub.3 CH.sub.2 --                                                                     Et--      Me-- C                                             521                                                                               m-O-i-Bu                                                                            CF.sub.3 CH.sub.2 --                                                                     Et--      Me-- C                                             522                                                                               p-O-i-Bu                                                                            CF.sub.3 CH.sub.2 --                                                                     Et--      Me-- C                                             523                                                                               o-OCF.sub.3                                                                         CF.sub.3 CH.sub.2 --                                                                     Et--      Me-- C                                             524                                                                               m-OCF.sub.3                                                                         CF.sub.3 CH.sub.2 --                                                                     Et--      Me-- C                                             525                                                                               p-OCF.sub.3                                                                         CF.sub.3 CH.sub.2 --                                                                     Et--      Me-- C                                             526                                                                               H    CF.sub.3 CH.sub.2 --                                                                     Et--      Me-- N                                             527                                                                               o-OCH.sub.3                                                                         CF.sub.3 CH.sub.2 --                                                                     Et--      Me-- N                                             528                                                                               m-OCH.sub.3                                                                         CF.sub.3 CH.sub.2 --                                                                     Et--      Me-- N                                             529                                                                               p-OCH.sub.3                                                                         CF.sub.3 CH.sub.2 --                                                                     Et--      Me-- N                                             530                                                                               o-Cl CF.sub.3 CH.sub.2 --                                                                     Et--      Me-- N                                             531                                                                               m-Cl CF.sub.3 CH.sub.2 --                                                                     Et--      Me-- N                                             532                                                                               p-Cl CF.sub.3 CH.sub.2 --                                                                     Et--      Me-- N                                             533                                                                               O-Br CF.sub.3 CH.sub.2 --                                                                     Et--      Me-- N                                             534                                                                               m-Br CF.sub.3 CH.sub.2 --                                                                     Et--      Me-- N                                             535                                                                               p-Br CF.sub.3 CH.sub.2 --                                                                     Et--      Me-- N                                             536                                                                               o-NH.sub.2                                                                          CF.sub.3 CH.sub.2 --                                                                     Et--      Me-- N                                             537                                                                               m-NH.sub.2                                                                          CF.sub.3 CH.sub.2 --                                                                     Et--      Me-- N                                             538                                                                               p-NH.sub.2                                                                          CF.sub.3 CH.sub.2 --                                                                     Et--      Me-- N                                             539                                                                               o-NO.sub.2                                                                          CF.sub.3 CH.sub.2 --                                                                     Et--      Me-- N                                             540                                                                               m-NO.sub.2                                                                          CF.sub.3 CH.sub.2 --                                                                     Et--      Me-- N                                             541                                                                               p-NO.sub.2                                                                          CF.sub.3 CH.sub.2 --                                                                     Et--      Me-- N                                             542                                                                               o-OC.sub.2 H.sub.5                                                                  CF.sub.3 CH.sub.2 --                                                                     Et--      Me-- N                                             543                                                                               m-OC.sub.2 H.sub.5                                                                  CF.sub.3 CH.sub.2 --                                                                     Et--      Me-- N                                             544                                                                               p-OC.sub.2 H.sub.5                                                                  CF.sub.3 CH.sub.2 --                                                                     Et--      Me-- N                                             545                                                                               p-I  CF.sub.3 CH.sub.2 --                                                                     Et--      Me-- N                                             546                                                                               o-O-n-Pr                                                                            CF.sub.3 CH.sub.2 --                                                                     Et--      Me-- N                                             547                                                                               m-O-n-Pr                                                                            CF.sub.3 CH.sub.2 --                                                                     Et--      Me-- N                                             548                                                                               p-O-n-Pr                                                                            CF.sub.3 CH.sub.2 --                                                                     Et--      Me-- N                                             549                                                                               o-O-i-Pr                                                                            CF.sub.3 CH.sub.2 --                                                                     Et--      Me-- N                                             550                                                                               m-O-i-Pr                                                                            CF.sub.3 CH.sub.2 --                                                                     Et--      Me-- N                                             551                                                                               p-O-i-Pr                                                                            CF.sub.3 CH.sub.2 --                                                                     Et--      Me-- N                                             552                                                                               o-O-n-Bu                                                                            CF.sub.3 CH.sub.2 --                                                                     Et--      Me-- N                                             553                                                                               m-O-n-Bu                                                                            CF.sub.3 CH.sub.2 --                                                                     Et--      Me-- N                                             554                                                                               p-O-n-Bu                                                                            CF.sub.3 CH.sub.2 --                                                                     Et--      Me-- N                                             555                                                                               o-O-i-Bu                                                                            CF.sub.3 CH.sub.2 --                                                                     Et--      Me-- N                                             556                                                                               m-O-i-Bu                                                                            CF.sub.3 CH.sub.2 --                                                                     Et--      Me-- N                                             557                                                                               p-O-i-Bu                                                                            CF.sub.3 CH.sub.2 --                                                                     Et--      Me-- N                                             558                                                                               o-OCF.sub.3                                                                         CF.sub.3 CH.sub.2 --                                                                     Et--      Me-- N                                             559                                                                               m-OCF.sub.3                                                                         CF.sub.3 CH.sub.2 --                                                                     Et--      Me-- N                                             560                                                                               p-OCF.sub.3                                                                         CF.sub.3 CH.sub.2 --                                                                     Et--      Me-- N                                             561                                                                               H    CF.sub.3 CH.sub.2 --                                                                     H         Me-- C                                             562                                                                               o-OCH.sub.3                                                                         CF.sub.3 CH.sub.2 --                                                                     H         Me-- C                                             563                                                                               m-OCH.sub.3                                                                         CF.sub.3 CH.sub.2 --                                                                     H         Me-- C                                             564                                                                               p-OCH.sub.3                                                                         CF.sub.3 CH.sub.2 --                                                                     H         Me-- C                                             565                                                                               o-Cl CF.sub.3 CH.sub.2 --                                                                     H         Me-- C                                             566                                                                               m-Cl CF.sub.3 CH.sub.2 --                                                                     H         Me-- C                                             567                                                                               p-Cl CF.sub.3 CH.sub.2 --                                                                     H         Me-- C                                             568                                                                               o-Br CF.sub.3 CH.sub.2 --                                                                     H         Me-- C                                             569                                                                               m-Br CF.sub.3 CH.sub.2 --                                                                     H         Me-- C                                             570                                                                               p-Br CF.sub.3 CH.sub.2 --                                                                     H         Me-- C                                             571                                                                               o-NH.sub.2                                                                          CF.sub.3 CH.sub.2 --                                                                     H         Me-- C                                             572                                                                               m-NH.sub.2                                                                          CF.sub.3 CH.sub.2 --                                                                     H         Me-- C                                             573                                                                               p-NH.sub.2                                                                          CF.sub.3 CH.sub.2 --                                                                     H         Me--                                               574                                                                               o-NO.sub.2                                                                          CF.sub.3 CH.sub.2 --                                                                     H         Me-- C                                             575                                                                               m-NO.sub.2                                                                          CF.sub.3 CH.sub.2 --                                                                     H         Me-- C                                             576                                                                               p-NO.sub.2                                                                          CF.sub.3 CH.sub.2 --                                                                     H         Me-- C                                             577                                                                               o-OC.sub.2 H.sub.5                                                                  CF.sub.3 CH.sub.2 --                                                                     H         Me-- C                                             578                                                                               m-OC.sub.2 H.sub.5                                                                  CF.sub.3 CH.sub.2 --                                                                     H         Me-- C                                             579                                                                               p-OC.sub.2 H.sub.5                                                                  CF.sub.3 CH.sub.2 --                                                                     H         Me-- C                                             580                                                                               p-I  CF.sub.3 CH.sub.2 --                                                                     H         Me-- C                                             581                                                                               o-O-n-Pr                                                                            CF.sub.3 CH.sub.2 --                                                                     H         Me-- C                                             582                                                                               m-O-n-Pr                                                                            CF.sub.3 CH.sub.2 --                                                                     H         Me-- C                                             583                                                                               p-O-n-Pr                                                                            CF.sub.3 CH.sub.2 --                                                                     H         Me-- C                                             584                                                                               o-O-i-Pr                                                                            CF.sub.3 CH.sub.2 --                                                                     H         Me-- C                                             585                                                                               m-O-i-Pr                                                                            CF.sub.3 CH.sub.2 --                                                                     H         Me-- C                                             586                                                                               p-O-i-Pr                                                                            CF.sub.3 CH.sub.2 --                                                                     H         Me-- C                                             587                                                                               o-O-n-Bu                                                                            CF.sub.3 CH.sub.2 --                                                                     H         Me-- C                                             588                                                                               m-O-n-Bu                                                                            CF.sub.3 CH.sub.2 --                                                                     H         Me-- C                                             589                                                                               p-O-n-Bu                                                                            CF.sub.3 CH.sub.2 --                                                                     H         Me-- C                                             590                                                                               o-O-i-Bu                                                                            CF.sub.3 CH.sub.2 --                                                                     H         Me-- C                                             591                                                                               m-O-i-Bu                                                                            CF.sub.3 CH.sub.2 --                                                                     H         Me-- C                                             592                                                                               p-O-i-Bu                                                                            CF.sub.3 CH.sub.2 --                                                                     H         Me-- C                                             593                                                                               o-OCF.sub.3                                                                         CF.sub.3 CH.sub.2 --                                                                     H         Me-- C                                             594                                                                               m-OCF.sub.3                                                                         CF.sub.3 CH.sub.2 --                                                                     H         Me-- C                                             595                                                                               p-OCF.sub.3                                                                         CF.sub.3 CH.sub.2 --                                                                     H         Me-- C                                             596                                                                               H    CF.sub.3 CH.sub.2 --                                                                     H         Me-- N                                             597                                                                               o-OCH.sub.3                                                                         CF.sub.3 CH.sub.2 --                                                                     H         Me-- N                                             598                                                                               m-OCH.sub.3                                                                         CF.sub.3 CH.sub.2 --                                                                     H         Me-- N                                             599                                                                               p-OCH.sub.3                                                                         CF.sub.3 CH.sub.2 --                                                                     H         Me-- N                                             600                                                                               o-Cl CF.sub.3 CH.sub.2 --                                                                     H         Me-- N                                             601                                                                               m-Cl CF.sub.3 CH.sub.2 --                                                                     H         Me-- N                                             602                                                                               p-Cl CF.sub.3 CH.sub.2 --                                                                     H         Me-- N                                             603                                                                               o-Br CF.sub.3 CH.sub.2 --                                                                     H         Me-- N                                             604                                                                               m-Br CF.sub.3 CH.sub.2 --                                                                     H         Me-- N                                             605                                                                               p-Br CF.sub.3 CH.sub.2 --                                                                     H         Me-- N                                             606                                                                               o-NH.sub.2                                                                          CF.sub.3 CH.sub.2 --                                                                     H         Me-- N                                             607                                                                               m-NH.sub.2                                                                          CF.sub.3 CH.sub.2 --                                                                     H         Me-- N                                             608                                                                               p-NH.sub.2                                                                          CF.sub.3 CH.sub.2 --                                                                     H         Me-- N                                             609                                                                               o-NO.sub.2                                                                          CF.sub.3 CH.sub.2 --                                                                     H         Me-- N                                             610                                                                               m-NO.sub.2                                                                          CF.sub.3 CH.sub.2 --                                                                     H         Me-- N                                             611                                                                               p-NO.sub.2                                                                          CF.sub.3 CH.sub.2 --                                                                     H         Me-- N                                             612                                                                               o-OC.sub.2 H.sub.5                                                                  CF.sub.3 CH.sub.2 --                                                                     H         Me-- N                                             613                                                                               m-OC.sub.2 H.sub.5                                                                  CF.sub.3 CH.sub.2 --                                                                     H         Me-- N                                             614                                                                               p-OC.sub.2 H.sub.5                                                                  CF.sub.3 CH.sub.2 --                                                                     H         Me-- N                                             615                                                                               p-I  CF.sub.3 CH.sub.2 --                                                                     H         Me-- N                                             616                                                                               o-O-n-Pr                                                                            CF.sub.3 CH.sub.2 --                                                                     H         Me-- N                                             617                                                                               m-O-n-Pr                                                                            CF.sub.3 CH.sub.2 --                                                                     H         Me-- N                                             618                                                                               p-O-n-Pr                                                                            CF.sub.3 CH.sub.2 --                                                                     H         Me-- N                                             619                                                                               o-O-i-Pr                                                                            CF.sub.3 CH.sub.2 --                                                                     H         Me-- N                                             620                                                                               m-O-i-Pr                                                                            CF.sub.3 CH.sub.2 --                                                                     H         Me-- N                                             621                                                                               p-O-i-Pr                                                                            CF.sub.3 CH.sub.2 --                                                                     H         Me-- N                                             622                                                                               o-O-n-Bu                                                                            CF.sub.3 CH.sub.2 --                                                                     H         Me-- N                                             623                                                                               m-O-n-Bu                                                                            CF.sub.3 CH.sub.2 --                                                                     H         Me-- N                                             624                                                                               p-O-n-Bu                                                                            CF.sub.3 CH.sub.2 --                                                                     H         Me-- N                                             625                                                                               o-O-i-Bu                                                                            CF.sub.3 CH.sub.2 --                                                                     H         Me-- N                                             626                                                                               m-O-i-Bu                                                                            CF.sub.3 CH.sub.2 --                                                                     H         Me-- N                                             627                                                                               p-O-i-Bu                                                                            CF.sub.3 CH.sub.2 --                                                                     H         Me-- N                                             628                                                                               o-OCF.sub.3                                                                         CF.sub.3 CH.sub.2 --                                                                     H         Me-- N                                             629                                                                               m-OCF.sub.3                                                                         CF.sub.3 CH.sub.2 --                                                                     H         Me-- N                                             630                                                                               p-OCF.sub.3                                                                         CF.sub.3 CH.sub.2 --                                                                     H         Me-- N                                             631                                                                               H    H         H         Me-- C                                             632                                                                               o-OCH.sub.3                                                                         H         H         Me-- C                                             633                                                                               m-OCH.sub.3                                                                         H         H         Me-- C                                             634                                                                               p-OCH.sub.3                                                                         H         H         Me-- C                                             635                                                                               o-Cl H         H         Me-- C                                             636                                                                               m-Cl H         H         Me-- C                                             637                                                                               p-Cl H         H         Me-- C                                             638                                                                               o-Br H         H         Me-- C                                             639                                                                               m-Br H         H         Me-- C                                             640                                                                               p-Br H         H         Me-- C                                             641                                                                               o-NH.sub.2                                                                          H         H         Me-- C                                             642                                                                               m-NH.sub.2                                                                          H         H         Me-- C                                             643                                                                               p-NH.sub.2                                                                          H         H         Me-- C                                             644                                                                               o-NO.sub.2                                                                          H         H         Me-- C                                             645                                                                               m-NO.sub.2                                                                          H         H         Me-- C                                             646                                                                               p-NO.sub.2                                                                          H         H         Me-- C                                             647                                                                               o-OC.sub.2 H.sub.5                                                                  H         H         Me-- C                                             648                                                                               m-OC.sub.2 H.sub.5                                                                  H         H         Me-- C                                             649                                                                               p-OC.sub.2 H.sub.5                                                                  H         H         Me-- C                                             650                                                                               p-I  H         H         Me-- C                                             651                                                                               o-O-n-Pr                                                                            H         H         Me-- C                                             652                                                                               m-O-n-Pr                                                                            H         H         Me-- C                                             653                                                                               p-O-n-Pr                                                                            H         H         Me-- C                                             654                                                                               o-O-i-Pr                                                                            H         H         Me-- C                                             655                                                                               m-O-i-Pr                                                                            H         H         Me-- C                                             656                                                                               p-O-i-Pr                                                                            H         H         Me-- C                                             657                                                                               o-O-n-Bu                                                                            H         H         Me-- C                                             658                                                                               m-O-n-Bu                                                                            H         H         Me-- C                                             659                                                                               p-O-n-Bu                                                                            H         H         Me-- C                                             660                                                                               o-O-i-Bu                                                                            H         H         Me-- C                                             661                                                                               m-O-i-Bu                                                                            H         H         Me-- C                                             662                                                                               p-O-i-Bu                                                                            H         H         Me-- C                                             663                                                                               o-OCF.sub.3                                                                         H         H         Me-- C                                             664                                                                               m-OCF.sub.3                                                                         H         H         Me-- C                                             665                                                                               p-OCF.sub.3                                                                         H         H         Me-- C                                             666                                                                               H    H         H         Me-- N                                             667                                                                               o-OCH.sub.3                                                                         H         H         Me-- N                                             668                                                                               m-OCH.sub.3                                                                         H         H         Me-- N                                             669                                                                               p-OCH.sub.3                                                                         H         H         Me-- N                                             670                                                                               o-Cl H         H         Me-- N                                             671                                                                               m-Cl H         H         Me-- N                                             672                                                                               p-Cl H         H         Me-- N                                             673                                                                               o-Br H         H         Me-- N                                             674                                                                               m-Br H         H         Me-- N                                             675                                                                               p-Br H         H         Me-- N                                             676                                                                               o-NH.sub.2                                                                          H         H         Me-- N                                             677                                                                               m-NH.sub.2                                                                          H         H         Me-- N                                             678                                                                               p-NH.sub.2                                                                          H         H         Me-- N                                             679                                                                               o-NO.sub.2                                                                          H         H         Me-- N                                             680                                                                               m-NO.sub.2                                                                          H         H         Me-- N                                             681                                                                               p-NO.sub.2                                                                          H         H         Me-- N                                             682                                                                               o-OC.sub.2 H.sub.5                                                                  H         H         Me-- N                                             683                                                                               m-OC.sub.2 H.sub.5                                                                  H         H         Me-- N                                             684                                                                               p-OC.sub.2 H.sub.5                                                                  H         H         Me-- N                                             685                                                                               p-I  H         H         Me-- N                                             686                                                                               o-O-n-Pr                                                                            H         H         Me-- N                                             687                                                                               m-O-n-Pr                                                                            H         H         Me-- N                                             688                                                                               p-O-n-Pr                                                                            H         H         Me-- N                                             689                                                                               o-O-i-Pr                                                                            H         H         Me-- N                                             690                                                                               m-O-i-Pr                                                                            H         H         Me-- N                                             691                                                                               p-O-i-Pr                                                                            H         H         Me-- N                                             692                                                                               o-O-n-Bu                                                                            H         H         Me-- N                                             693                                                                               m-O-n-Bu                                                                            H         H         Me-- N                                             694                                                                               p-O-n-Bu                                                                            H         H         Me-- N                                             695                                                                               o-O-i-Bu                                                                            H         H         Me-- N                                             696                                                                               m-O-i-Bu                                                                            H         H         Me-- N                                             697                                                                               p-O-i-Bu                                                                            H         H         Me-- N                                             698                                                                               o-OCF.sub.3                                                                         H         H         Me-- N                                             699                                                                               m-OCF.sub.3                                                                         H         H         Me-- N                                             700                                                                               p-OCF.sub.3                                                                         H         H         Me-- N                                             701                                                                               H    CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     --CH.sub.2 F                                                                        C                                             702                                                                               o-OCH.sub.3                                                                         CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     --CH.sub.2 F                                                                        C                                             703                                                                               m-OCH.sub.3                                                                         CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     --CH.sub.2 F                                                                        C                                             704                                                                               p-OCH.sub.3                                                                         CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     --CH.sub.2 F                                                                        C                                             705                                                                               o-Cl CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     --CH.sub.2 F                                                                        C                                             706                                                                               m-Cl CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     --CH.sub.2 F                                                                        C                                             707                                                                               p-Cl CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     --CH.sub.2 F                                                                        C                                             708                                                                               o-Br CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     --CH.sub.2 F                                                                        C                                             709                                                                               m-Br CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     --CH.sub.2 F                                                                        C                                             710                                                                               p-Br CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     --CH.sub.2 F                                                                        C                                             711                                                                               o-NH.sub.2                                                                          CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     --CH.sub.2 F                                                                        C                                             712                                                                               m-NH.sub.2                                                                          CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     --CH.sub.2 F                                                                        C                                             713                                                                               p-NH.sub.2                                                                          CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     --CH.sub.2 F                                                                        C                                             714                                                                               o-NO.sub.2                                                                          CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     --CH.sub.2 F                                                                        C                                             715                                                                               m-NO.sub.2                                                                          CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     --CH.sub.2 F                                                                        C                                             716                                                                               p-NO.sub.2                                                                          CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     --CH.sub.2 F                                                                        C                                             717                                                                               o-OC.sub.2 H.sub.5                                                                  CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     --CH.sub.2 F                                                                        C                                             718                                                                               m-OC.sub.2 H.sub.5                                                                  CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     --CH.sub.2 F                                                                        C                                             719                                                                               p-OC.sub.2 H.sub.5                                                                  CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     --CH.sub.2 F                                                                        C                                             720                                                                               p-I  CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     --CH.sub.2 F                                                                        C                                             721                                                                               o-O-n-Pr                                                                            CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     --CH.sub.2 F                                                                        C                                             722                                                                               m-O-n-Fr                                                                            CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     --CH.sub.2 F                                                                        C                                             723                                                                               p-O-n-Pr                                                                            CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     --CH.sub.2 F                                                                        C                                             724                                                                               o-O-i-Pr                                                                            CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     --CH.sub.2 F                                                                        C                                             725                                                                               m-O-i-Pr                                                                            CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     --CH.sub.2 F                                                                        C                                             726                                                                               p-O-i-Pr                                                                            CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     --CH.sub.2 F                                                                        C                                             727                                                                               o-O-n-Bu                                                                            CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     --CH.sub.2 F                                                                        C                                             728                                                                               m-O-n-Bu                                                                            CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     --CH.sub.2 F                                                                        C                                             729                                                                               p-O-n-Bu                                                                            CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     --CH.sub.2 F                                                                        C                                             730                                                                               o-O-i-Bu                                                                            CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     --CH.sub.2 F                                                                        C                                             731                                                                               m-O-i-Bu                                                                            CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     --CH.sub.2 F                                                                        C                                             732                                                                               p-O-i-Bu                                                                            CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     --CH.sub.2 F                                                                        C                                             733                                                                               o-OCF.sub.3                                                                         CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     --CH.sub.2 F                                                                        C                                             734                                                                               m-OCF.sub.3                                                                         CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     --CH.sub.2 F                                                                        C                                             735                                                                               p-OCF.sub.3                                                                         CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     --CH.sub.2 F                                                                        C                                             736                                                                               H    CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     --CH.sub.2 F                                                                        N                                             737                                                                               o-OCH.sub.3                                                                         CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     --CH.sub.2 F                                                                        N                                             738                                                                               m-OCH.sub.3                                                                         CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     --CH.sub.2 F                                                                        N                                             739                                                                               p-OCH.sub.3                                                                         CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     --CH.sub.2 F                                                                        N                                             740                                                                               o-Cl CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     --CH.sub.2 F                                                                        N                                             741                                                                               m-Cl CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     --CH.sub.2 F                                                                        N                                             742                                                                               p-Cl CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     --CH.sub.2 F                                                                        N                                             743                                                                               o-Br CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     --CH.sub.2 F                                                                        N                                             744                                                                               m-Br CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     --CH.sub.2 F                                                                        N                                             745                                                                               p-Br CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     --CH.sub.2 F                                                                        N                                             746                                                                               o-NH.sub.2                                                                          CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     --CH.sub.2 F                                                                        N                                             747                                                                               m-NH.sub.2                                                                          CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     --CH.sub.2 F                                                                        N                                             748                                                                               p-NH.sub.2                                                                          CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     --CH.sub.2 F                                                                        N                                             749                                                                               o-NO.sub.2                                                                          CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     --CH.sub.2 F                                                                        N                                             750                                                                               m-NO.sub.2                                                                          CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     --CH.sub.2 F                                                                        N                                             751                                                                               p-NO.sub.2                                                                          CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     --CH.sub.2 F                                                                        N                                             752                                                                               o-OC.sub.2 H.sub.5                                                                  CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     --CH.sub.2 F                                                                        N                                             753                                                                               m-OC.sub.2 H.sub.5                                                                  CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     --CH.sub.2 F                                                                        N                                             754                                                                               p-OC.sub.2 H.sub.5                                                                  CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     --CH.sub.2 F                                                                        N                                             755                                                                               p-I  CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     --CH.sub.2 F                                                                        N                                             756                                                                               o-O-n-Pr                                                                            CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     --CH.sub.2 F                                                                        N                                             757                                                                               m-O-n-Pr                                                                            CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     --CH.sub.2 F                                                                        N                                             758                                                                               p-O-n-Pr                                                                            CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     --CH.sub.2 F                                                                        N                                             759                                                                               o-O-i-Pr                                                                            CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     --CH.sub.2 F                                                                        N                                             760                                                                               m-O-i-Pr                                                                            CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     --CH.sub.2 F                                                                        N                                             761                                                                               p-O-i-Pr                                                                            CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     --CH.sub.2 F                                                                        N                                             762                                                                               o-O-n-Bu                                                                            CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     --CH.sub.2 F                                                                        N                                             763                                                                               m-O-n-Bu                                                                            CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     --CH.sub.2 F                                                                        N                                             764                                                                               p-O-n-Bu                                                                            CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     --CH.sub.2 F                                                                        N                                             765                                                                               o-O-i-Bu                                                                            CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     --CH.sub.2 F                                                                        N                                             766                                                                               m-O-i-Bu                                                                            CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     --CH.sub.2 F                                                                        N                                             767                                                                               p-O-i-Bu                                                                            CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     --CH.sub.2 F                                                                        N                                             768                                                                               o-OCF.sub.3                                                                         CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     --CH.sub.2 F                                                                        N                                             769                                                                               m-OCF.sub.3                                                                         CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     --CH.sub.2 F                                                                        N                                             770                                                                               p-OCF.sub.3                                                                         CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     --CH.sub.2 F                                                                        N                                             771                                                                               H    CF.sub.3 CH.sub.2 --                                                                     Me--      --CH.sub.2 F                                                                        C                                             772                                                                               o-OCH.sub.3                                                                         CF.sub.3 CH.sub.2 --                                                                     Me--      --CH.sub.2 F                                                                        C                                             773                                                                               m-OCH.sub.3                                                                         CF.sub.3 CH.sub.2 --                                                                     Me--      --CH.sub.2 F                                                                        C                                             774                                                                               p-OCH.sub.3                                                                         CF.sub.3 CH.sub.2 --                                                                     Me--      --CH.sub.2 F                                                                        C                                             775                                                                               o-Cl CF.sub.3 CH.sub.2 --                                                                     Me--      --CH.sub.2 F                                                                        C                                             776                                                                               m-Cl CF.sub.3 CH.sub.2 --                                                                     Me--      --CH.sub.2 F                                                                        C                                             777                                                                               p-Cl CF.sub.3 CH.sub.2 --                                                                     Me--      --CH.sub.2 F                                                                        C                                             778                                                                               o-Br CF.sub.3 CH.sub.2 --                                                                     Me--      --CH.sub.2 F                                                                        C                                             779                                                                               m-Br CF.sub.3 CH.sub.2 --                                                                     Me--      --CH.sub.2 F                                                                        C                                             780                                                                               p-Br CF.sub.3 CH.sub.2 --                                                                     Me--      --CH.sub.2 F                                                                        C                                             781                                                                               o-NH.sub.2                                                                          CF.sub.3 CH.sub.2 --                                                                     Me--      --CH.sub.2 F                                                                        C                                             782                                                                               m-NH.sub.2                                                                          CF.sub.3 CH.sub.2 --                                                                     Me--      --CH.sub.2 F                                                                        C                                             783                                                                               p-NH.sub.2                                                                          CF.sub.3 CH.sub.2 --                                                                     Me--      --CH.sub.2 F                                                                        C                                             784                                                                               o-NO.sub.2                                                                          CF.sub.3 CH.sub.2 --                                                                     Me--      --CH.sub.2 F                                                                        C                                             785                                                                               m-NO.sub.2                                                                          CF.sub.3 CH.sub.2 --                                                                     Me--      --CH.sub.2 F                                                                        C                                             786                                                                               p-NO.sub.2                                                                          CF.sub.3 CH.sub.2 --                                                                     Me--      --CH.sub.2 F                                                                        C                                             787                                                                               o-OC.sub.2 H.sub.5                                                                  CF.sub.3 CH.sub.2 --                                                                     Me--      --CH.sub.2 F                                                                        C                                             788                                                                               m-OC.sub.2 H.sub.5                                                                  CF.sub.3 CH.sub.2 --                                                                     Me--      --CH.sub.2 F                                                                        C                                             789                                                                               p-OC.sub.2 H.sub.5                                                                  CF.sub.3 CH.sub.2 --                                                                     Me--      --CH.sub.2 F                                                                        C                                             790                                                                               p-I  CF.sub.3 CH.sub.2 --                                                                     Me--      --CH.sub.2 F                                                                        C                                             791                                                                               o-O-n-Pr                                                                            CF.sub.3 CH.sub.2 --                                                                     Me--      --CH.sub.2 F                                                                        C                                             792                                                                               m-O-n-Pr                                                                            CF.sub.3 CH.sub.2 --                                                                     Me--      --CH.sub.2 F                                                                        C                                             793                                                                               p-O-n-Pr                                                                            CF.sub.3 CH.sub.2 --                                                                     Me--      --CH.sub.2 F                                                                        C                                             794                                                                               o-O-i-Pr                                                                            CF.sub.3 CH.sub.2 --                                                                     Me--      --CH.sub.2 F                                                                        C                                             795                                                                               m-O-i-Pr                                                                            CF.sub.3 CH.sub.2 --                                                                     Me--      --CH.sub.2 F                                                                        C                                             796                                                                               p-O-i-Pr                                                                            CF.sub.3 CH.sub.2 --                                                                     Me--      --CH.sub.2 F                                                                        C                                             797                                                                               o-O-n-Bu                                                                            CF.sub.3 CH.sub.2 --                                                                     Me--      --CH.sub.2 F                                                                        C                                             798                                                                               m-O-n-Bu                                                                            CF.sub.3 CH.sub.2 --                                                                     Me--      --CH.sub.2 F                                                                        C                                             799                                                                               p-O-n-Bu                                                                            CF.sub.3 CH.sub.2 --                                                                     Me--      --CH.sub.2 F                                                                        C                                             800                                                                               o-O-i-Bu                                                                            CF.sub.3 CH.sub.2 --                                                                     Me--      --CH.sub.2 F                                                                        C                                             801                                                                               m-O-i-Bu                                                                            CF.sub.3 CH.sub.2 --                                                                     Me--      --CH.sub.2 F                                                                        C                                             802                                                                               p-O-i-Bu                                                                            CF.sub.3 CH.sub.2 --                                                                     Me--      --CH.sub.2 F                                                                        C                                             803                                                                               o-OCF.sub.3                                                                         CF.sub.3 CH.sub.2 --                                                                     Me--      --CH.sub.2 F                                                                        C                                             804                                                                               m-OCF.sub.3                                                                         CF.sub.3 CH.sub.2 --                                                                     Me--      --CH.sub.2 F                                                                        C                                             805                                                                               p-OCF.sub.3                                                                         CF.sub.3 CH.sub.2 --                                                                     Me--      --CH.sub.2 F                                                                        C                                             806                                                                               H    CF.sub.3 CH.sub.2 --                                                                     Me--      --CH.sub.2 F                                                                        N                                             807                                                                               o-OCH.sub.3                                                                         CF.sub.3 CH.sub.2 --                                                                     Me--      --CH.sub.2 F                                                                        N                                             808                                                                               m-OCH.sub.3                                                                         CF.sub.3 CH.sub.2 --                                                                     Me--      --CH.sub.2 F                                                                        N                                             809                                                                               p-OCH.sub.3                                                                         CF.sub.3 CH.sub.2 --                                                                     Me--      --CH.sub.2 F                                                                        N                                             810                                                                               o-Cl CF.sub.3 CH.sub.2 --                                                                     Me--      --CH.sub.2 F                                                                        N                                             811                                                                               m-Cl CF.sub.3 CH.sub.2 --                                                                     Me--      --CH.sub.2 F                                                                        N                                             812                                                                               p-Cl CF.sub.3 CH.sub.2 --                                                                     Me--      --CH.sub.2 F                                                                        N                                             813                                                                               o-Br CF.sub.3 CH.sub.2 --                                                                     Me--      --CH.sub.2 F                                                                        N                                             814                                                                               m-Br CF.sub.3 CH.sub.2 --                                                                     Me--      --CH.sub.2 F                                                                        N                                             815                                                                               p-Br CF.sub.3 CH.sub.2 --                                                                     Me--      --CH.sub.2 F                                                                        N                                             816                                                                               o-NH.sub.2                                                                          CF.sub.3 CH.sub.2 --                                                                     Me--      --CH.sub.2 F                                                                        N                                             817                                                                               m-NH.sub.2                                                                          CF.sub.3 CH.sub.2 --                                                                     Me--      --CH.sub.2 F                                                                        N                                             818                                                                               p-NH.sub.2                                                                          CF.sub.3 CH.sub.2 --                                                                     Me--      --CH.sub.2 F                                                                        N                                             819                                                                               o-NO.sub.2                                                                          CF.sub.3 CH.sub.2 --                                                                     Me--      --CH.sub.2 F                                                                        N                                             820                                                                               m-NO.sub.2                                                                          CF.sub.3 CH.sub.2 --                                                                     Me--      --CH.sub.2 F                                                                        N                                             821                                                                               p-NO.sub.2                                                                          CF.sub.3 CH.sub.2 --                                                                     Me--      --CH.sub.2 F                                                                        N                                             822                                                                               o-OC.sub.2 H.sub.5                                                                  CF.sub.3 CH.sub.2 --                                                                     Me--      --CH.sub.2 F                                                                        N                                             823                                                                               m-OC.sub.2 H.sub.5                                                                  CF.sub.3 CH.sub.2 --                                                                     Me--      --CH.sub.2 F                                                                        N                                             824                                                                               p-OC.sub.2 H.sub.5                                                                  CF.sub.3 CH.sub.2 --                                                                     Me--      --CH.sub.2 F                                                                        N                                             825                                                                               p-I  CF.sub.3 CH.sub.2 --                                                                     Me--      --CH.sub.2 F                                                                        N                                             826                                                                               o-O-n-Pr                                                                            CF.sub.3 CH.sub.2 --                                                                     Me--      --CH.sub.2 F                                                                        N                                             827                                                                               m-O-n-Pr                                                                            CF.sub.3 CH.sub.2 --                                                                     Me--      --CH.sub.2 F                                                                        N                                             828                                                                               p-O-n-Pr                                                                            CF.sub.3 CH.sub.2 --                                                                     Me--      --CH.sub.2 F                                                                        N                                             829                                                                               o-O-i-Pr                                                                            CF.sub.3 CH.sub.2 --                                                                     Me--      --CH.sub.2 F                                                                        N                                             830                                                                               m-O-i-Pr                                                                            CF.sub.3 CH.sub.2 --                                                                     Me--      --CH.sub.2 F                                                                        N                                             831                                                                               p-O-i-Pr                                                                            CF.sub.3 CH.sub.2 --                                                                     Me--      --CH.sub.2 F                                                                        N                                             832                                                                               o-O-n-Du                                                                            CF.sub.3 CH.sub.2 --                                                                     Me--      --CH.sub.2 F                                                                        N                                             833                                                                               m-O-n-Bu                                                                            CF.sub.3 CH.sub.2 --                                                                     Me--      --CH.sub.2 F                                                                        N                                             834                                                                               p-O-n-Bu                                                                            CF.sub.3 CH.sub.2 --                                                                     Me--      --CH.sub.2 F                                                                        N                                             835                                                                               o-O-i-Bu                                                                            CF.sub.3 CH.sub.2 --                                                                     Me--      --CH.sub.2 F                                                                        N                                             836                                                                               m-O-i-Bu                                                                            CF.sub.3 CH.sub.2 --                                                                     Me--      --CH.sub.2 F                                                                        N                                             837                                                                               p-O-i-Bu                                                                            CF.sub.3 CH.sub.2 --                                                                     Me--      --CH.sub.2 F                                                                        N                                             838                                                                               o-OCF.sub.3                                                                         CF.sub.3 CH.sub.2 --                                                                     Me--      --CH.sub.2 F                                                                        N                                             839                                                                               m-OCF.sub.3                                                                         CF.sub.3 CH.sub.2 --                                                                     Me--      --CH.sub.2 F                                                                        N                                             840                                                                               p-OCF.sub.3                                                                         CF.sub.3 CH.sub.2 --                                                                     Me--      --CH.sub.2 F                                                                        N                                             841                                                                               H    F3CH.sub.2 --                                                                            Et--      --CH.sub.2 F                                                                        C                                             842                                                                               o-OCH.sub.3                                                                         CF.sub.3 CH.sub.2 --                                                                     Et--      --CH.sub.2 F                                                                        C                                             843                                                                               m-OCH.sub.3                                                                         CF.sub.3 CH.sub.2 --                                                                     Et--      --CH.sub.2 F                                                                        C                                             844                                                                               p-OCH.sub.3                                                                         CF.sub.3 CH.sub.2 --                                                                     Et--      --CH.sub.2 F                                                                        C                                             845                                                                               o-Cl CF.sub.3 CH.sub.2 --                                                                     Et--      --CH.sub.2 F                                                                        C                                             846                                                                               m-Cl CF.sub.3 CH.sub.2 --                                                                     Et--      --CH.sub.2 F                                                                        C                                             847                                                                               p-Cl CF.sub.3 CH.sub.2 --                                                                     Et--      --CH.sub.2 F                                                                        C                                             848                                                                               o-Br CF.sub.3 CH.sub.2 --                                                                     Et--      --CH.sub.2 F                                                                        C                                             849                                                                               m-Br CF.sub.3 CH.sub.2 --                                                                     Et--      --CH.sub.2 F                                                                        C                                             850                                                                               p-Br CF.sub.3 CH.sub.2 --                                                                     Et--      --CH.sub.2 F                                                                        C                                             851                                                                               o-NH.sub.2                                                                          CF.sub.3 CH.sub.2 --                                                                     Et--      --CH.sub.2 F                                                                        C                                             852                                                                               m-NH.sub.2                                                                          CF.sub.3 CH.sub.2 --                                                                     Et--      --CH.sub.2 F                                                                        C                                             853                                                                               p-NH.sub.2                                                                          CF.sub.3 CH.sub.2 --                                                                     Et--      --CH.sub.2 F                                                                        C                                             854                                                                               o-NO.sub.2                                                                          CF.sub.3 CH.sub.2 --                                                                     Et--      --CH.sub.2 F                                                                        C                                             855                                                                               m-NO.sub.2                                                                          CF.sub.3 CH.sub.2 --                                                                     Et--      --CH.sub.2 F                                                                        C                                             856                                                                               p-NO.sub.2                                                                          CF.sub.3 CH.sub.2 --                                                                     Et--      --CH.sub.2 F                                                                        C                                             857                                                                               o-OC.sub.2 H.sub.5                                                                  CF.sub.3 CH.sub.2 --                                                                     Et--      --CH.sub.2 F                                                                        C                                             858                                                                               m-OC.sub.2 H.sub.5                                                                  CF.sub.3 CH.sub.2 --                                                                     Et--      --CH.sub.2 F                                                                        C                                             859                                                                               p-OC.sub.2 H.sub.5                                                                  CF.sub.3 CH.sub.2 --                                                                     Et--      --CH.sub.2 F                                                                        C                                             860                                                                               p-I  CF.sub.3 CH.sub.2 --                                                                     Et--      --CH.sub.2 F                                                                        C                                             861                                                                               o-O-n-Pr                                                                            CF.sub.3 CH.sub.2 --                                                                     Et--      --CH.sub.2 F                                                                        C                                             862                                                                               m-O-n-Pr                                                                            CF.sub.3 CH.sub.2 --                                                                     Et--      --CH.sub.2 F                                                                        C                                             863                                                                               p-O-n-Pr                                                                            CF.sub.3 CH.sub.2 --                                                                     Et--      --CH.sub.2 F                                                                        C                                             864                                                                               o-O-i-Pr                                                                            CF.sub.3 CH.sub.2 --                                                                     Et--      --CH.sub.2 F                                                                        C                                             865                                                                               m-O-i-Pr                                                                            CF.sub.3 CH.sub.2 --                                                                     Et--      --CH.sub.2 F                                                                        C                                             866                                                                               p-O-i-Pr                                                                            CF.sub.3 CH.sub.2 --                                                                     Et--      --CH.sub.2 F                                                                        C                                             867                                                                               o-O-n-Bu                                                                            CF.sub.3 CH.sub.2 --                                                                     Et--      --CH.sub.2 F                                                                        C                                             868                                                                               m-O-n-Bu                                                                            CF.sub.3 CH.sub.2 --                                                                     Et--      --CH.sub.2 F                                                                        C                                             869                                                                               p-O-n-Bu                                                                            CF.sub.3 CH.sub.2 --                                                                     Et--      --CH.sub.2 F                                                                        C                                             870                                                                               o-O-i-Bu                                                                            CF.sub.3 CH.sub.2 --                                                                     Et--      --CH.sub.2 F                                                                        C                                             871                                                                               m-O-i-Bu                                                                            CF.sub.3 CH.sub.2 --                                                                     Et--      --CH.sub.2 F                                                                        C                                             872                                                                               p-O-i-Bu                                                                            CF.sub.3 CH.sub.2 --                                                                     Et--      --CH.sub.2 F                                                                        C                                             873                                                                               o-OCF.sub.3                                                                         CF.sub.3 CH.sub.2 --                                                                     Et--      --CH.sub.2 F                                                                        C                                             874                                                                               m-OCF.sub.3                                                                         CF.sub.3 CH.sub.2 --                                                                     Et--      --CH.sub.2 F                                                                        C                                             875                                                                               p-OCF.sub.3                                                                         CF.sub.3 CH.sub.2 --                                                                     Et--      --CH.sub.2 F                                                                        C                                             876                                                                               H    CF.sub.3 CH.sub.2 --                                                                     Et--      --CH.sub.2 F                                                                        N                                             877                                                                               o-OCH.sub.3                                                                         CF.sub.3 CH.sub.2 --                                                                     Et--      --CH.sub.2 F                                                                        N                                             878                                                                               m-OCH.sub.3                                                                         CF.sub.3 CH.sub.2 --                                                                     Et--      --CH.sub.2 F                                                                        N                                             879                                                                               p-OCH.sub.3                                                                         CF.sub.3 CH.sub.2 --                                                                     Et--      --CH.sub.2 F                                                                        N                                             880                                                                               o-Cl CF.sub.3 CH.sub.2 --                                                                     Et--      --CH.sub.2 F                                                                        N                                             881                                                                               m-Cl CF.sub.3 CH.sub.2 --                                                                     Et--      --CH.sub.2 F                                                                        N                                             882                                                                               p-CJ CF.sub.3 CH.sub.2 --                                                                     Et--      --CH.sub.2 F                                                                        N                                             883                                                                               o-Br CF.sub.3 CH.sub.2 --                                                                     Et--      --CH.sub.2 F                                                                        N                                             884                                                                               m-Br CF.sub.3 CH.sub.2 --                                                                     Et--      --CH.sub.2 F                                                                        N                                             885                                                                               p-Br CF.sub.3 CH.sub.2 --                                                                     Et--      --CH.sub.2 F                                                                        N                                             886                                                                               o-NH.sub.2                                                                          CF.sub.3 CH.sub.2 --                                                                     Et--      --CH.sub.2 F                                                                        N                                             887                                                                               m-NH.sub.2                                                                          CF.sub.3 CH.sub.2 --                                                                     Et--      --CH.sub.2 F                                                                        N                                             888                                                                               p-NH.sub.2                                                                          CF.sub.3 CH.sub.2 --                                                                     Et--      --CH.sub.2 F                                                                        N                                             889                                                                               o-NO.sub.2                                                                          CF.sub.3 CH.sub.2 --                                                                     Et--      --CH.sub.2 F                                                                        N                                             890                                                                               m-NO.sub.2                                                                          CF.sub.3 CH.sub.2 --                                                                     Et--      --CH.sub.2 F                                                                        N                                             891                                                                               p-NO.sub.2                                                                          CF.sub.3 CH.sub.2 --                                                                     Et--      --CH.sub.2 F                                                                        N                                             892                                                                               o-OC.sub.2 H.sub.5                                                                  CF.sub.3 CH.sub.2 --                                                                     Et--      --CH.sub.2 F                                                                        N                                             893                                                                               m-OC.sub.2 H.sub.5                                                                  CF.sub.3 CH.sub.2 --                                                                     Et--      --CH.sub.2 F                                                                        N                                             894                                                                               p-OC.sub.2 H.sub.5                                                                  CF.sub.3 CH.sub.2 --                                                                     Et--      --CH.sub.2 F                                                                        N                                             895                                                                               p-I  CF.sub.3 CH.sub.2 --                                                                     Et--      --CH.sub.2 F                                                                        N                                             896                                                                               o-O-n-Pr                                                                            CF.sub.3 CH.sub.2 --                                                                     Et--      --CH.sub.2 F                                                                        N                                             897                                                                               m-O-n-Pr                                                                            CF.sub.3 CH.sub.2 --                                                                     Et--      --CH.sub.2 F                                                                        N                                             898                                                                               p-O-n-Pr                                                                            CF.sub.3 CH.sub.2 --                                                                     Et--      --CH.sub.2 F                                                                        N                                             899                                                                               o-O-i-Pr                                                                            CF.sub.3 CH.sub.2 --                                                                     Et--      --CH.sub.2 F                                                                        N                                             900                                                                               m-O-i-Pr                                                                            CF.sub.3 CH.sub.2 --                                                                     Et--      --CH.sub.2 F                                                                        N                                             901                                                                               p-O-i-Pr                                                                            CF.sub.3 CH.sub.2 --                                                                     Et--      --CH.sub.2 F                                                                        N                                             902                                                                               o-O-n-Bu                                                                            CF.sub.3 CH.sub.2 --                                                                     Et--      --CH.sub.2 F                                                                        N                                             903                                                                               m-O-n-Bu                                                                            CF.sub.3 CH.sub.2 --                                                                     Et--      --CH.sub.2 F                                                                        N                                             904                                                                               p-O-n-Bu                                                                            CF.sub.3 CH.sub.2 --                                                                     Et--      --CH.sub.2 F                                                                        N                                             905                                                                               o-O-i-Bu                                                                            CF.sub.3 CH.sub.2 --                                                                     Et--      --CH.sub.2 F                                                                        N                                             906                                                                               m-O-i-Bu                                                                            CF.sub.3 CH.sub.2 --                                                                     Et--      --CH.sub.2 F                                                                        N                                             907                                                                               p-O-i-Bu                                                                            CF.sub.3 CH.sub.2 --                                                                     Et--      --CH.sub.2 F                                                                        N                                             908                                                                               o-OCF.sub.3                                                                         CF.sub.3 CH.sub.2 --                                                                     Et--      --CH.sub.2 F                                                                        N                                             909                                                                               m-OCF.sub.3                                                                         CF.sub.3 CH.sub.2 --                                                                     Et--      --CH.sub.2 F                                                                        N                                             910                                                                               p-OCF.sub.3                                                                         CF.sub.3 CH.sub.2 --                                                                     Et--      --CH.sub.2 F                                                                        N                                             911                                                                               H    CF.sub.3 CH.sub.2 --                                                                     H         --CH.sub.2 F                                                                        C                                             912                                                                               o-OCH.sub.3                                                                         CF.sub.3 CH.sub.2 --                                                                     H         --CH.sub.2 F                                                                        C                                             913                                                                               m-OCH.sub.3                                                                         CF.sub.3 CH.sub.2 --                                                                     H         --CH.sub.2 F                                                                        C                                             914                                                                               p-OCH.sub.3                                                                         CF.sub.3 CH.sub.2 --                                                                     H         --CH.sub.2 F                                                                        C                                             915                                                                               o-Cl CF.sub.3 CH.sub.2 --                                                                     H         --CH.sub.2 F                                                                        C                                             916                                                                               m-Cl CF.sub.3 CH.sub.2 --                                                                     H         --CH.sub.2 F                                                                        C                                             917                                                                               p-Cl CF.sub.3 CH.sub.2 --                                                                     H         --CH.sub.2 F                                                                        C                                             918                                                                               o-Br CF.sub.3 CH.sub.2 --                                                                     H         --CH.sub.2 F                                                                        C                                             919                                                                               m-Br CF.sub.3 CH.sub.2 --                                                                     H         --CH.sub.2 F                                                                        C                                             920                                                                               p-Br CF.sub.3 CH.sub.2 --                                                                     H         --CH.sub.2 F                                                                        C                                             921                                                                               o-NH.sub.2                                                                          CF.sub.3 CH.sub.2 --                                                                     H         --CH.sub.2 F                                                                        C                                             922                                                                               m-NH.sub.2                                                                          CF.sub.3 CH.sub.2 --                                                                     H         --CH.sub.2 F                                                                        C                                             923                                                                               p-NH.sub.2                                                                          CF.sub.3 CH.sub.2 --                                                                     H         --CH.sub.2 F                                                                        C                                             924                                                                               o-NO.sub.2                                                                          CF.sub.3 CH.sub.2 --                                                                     H         --CH.sub.2 F                                                                        C                                             925                                                                               m-NO.sub.2                                                                          CF.sub.3 CH.sub.2 --                                                                     H         --CH.sub.2 F                                                                        C                                             926                                                                               p-NO.sub.2                                                                          CF.sub.3 CH.sub.2 --                                                                     H         --CH.sub.2 F                                                                        C                                             927                                                                               o-OC.sub.2 H.sub.5                                                                  CF.sub.3 CH.sub.2 --                                                                     H         --CH.sub.2 F                                                                        C                                             928                                                                               m-OC.sub.2 H.sub.5                                                                  CF.sub.3 CH.sub.2 --                                                                     H         --CH.sub.2 F                                                                        C                                             929                                                                               p-OC.sub.2 H.sub.5                                                                  CF.sub.3 CH.sub.2 --                                                                     H         --CH.sub.2 F                                                                        C                                             930                                                                               p-I  CF.sub.3 CH.sub.2 --                                                                     H         --CH.sub.2 F                                                                        C                                             931                                                                               o-O-n-Pr                                                                            CF.sub.3 CH.sub.2 --                                                                     H         --CH.sub.2 F                                                                        C                                             932                                                                               m-O-n-Pr                                                                            CF.sub.3 CH.sub.2 --                                                                     H         --CH.sub.2 F                                                                        C                                             933                                                                               p-O-n-Pr                                                                            CF.sub.3 CH.sub.2 --                                                                     H         --CH.sub.2 F                                                                        C                                             934                                                                               o-O-i-Pr                                                                            CF.sub.3 CH.sub.2 --                                                                     H         --CH.sub.2 F                                                                        C                                             935                                                                               m-O-i-Pr                                                                            CF.sub.3 CH.sub.2 --                                                                     H         --CH.sub.2 F                                                                        C                                             936                                                                               p-O-i-Pr                                                                            CF.sub.3 CH.sub.2 --                                                                     H         --CH.sub.2 F                                                                        C                                             937                                                                               o-O-n-Bu                                                                            CF.sub.3 CH.sub.2 --                                                                     H         --CH.sub.2 F                                                                        C                                             938                                                                               m-O-n-Bu                                                                            CF.sub.3 CH.sub.2 --                                                                     H         --CH.sub.2 F                                                                        C                                             939                                                                               p-O-n-Bu                                                                            CF.sub.3 CH.sub.2 --                                                                     H         --CH.sub.2 F                                                                        C                                             940                                                                               o-O-i-Bu                                                                            CF.sub.3 CH.sub.2 --                                                                     H         --CH.sub.2 F                                                                        C                                             941                                                                               m-O-i-Bu                                                                            CF.sub.3 CH.sub.2 --                                                                     H         --CH.sub.2 F                                                                        C                                             942                                                                               p-O-i-Bu                                                                            CF.sub.3 CH.sub.2 --                                                                     H         --CH.sub.2 F                                                                        C                                             943                                                                               o-OCF.sub.3                                                                         CF.sub.3 CH.sub.2 --                                                                     H         --CH.sub.2 F                                                                        C                                             944                                                                               m-OCF.sub.3                                                                         CF.sub.3 CH.sub.2 --                                                                     H         --CH.sub.2 F                                                                        C                                             945                                                                               p-OCF.sub.3                                                                         CF.sub.3 CH.sub.2 --                                                                     H         --CH.sub.2 F                                                                        C                                             946                                                                               H    CF.sub.3 CH.sub.2 --                                                                     H         --CH.sub.2 F                                                                        N                                             947                                                                               o-OCH.sub.3                                                                         CF.sub.3 CH.sub.2 --                                                                     H         --CH.sub.2 F                                                                        N                                             948                                                                               m-OCH.sub.3                                                                         CF.sub.3 CH2                                                                             H         --CH.sub.2 F                                                                        N                                             949                                                                               p-OCH.sub.3                                                                         CF.sub.3 CH.sub.2 --                                                                     H         --CH.sub.2 F                                                                        N                                             950                                                                               o-Cl CF.sub.3 CH.sub.2 --                                                                     H         --CH.sub.2 F                                                                        N                                             951                                                                               m-Cl CF.sub.3 CH.sub.2 --                                                                     H         --CH.sub.2 F                                                                        N                                             952                                                                               p-Cl CF.sub.3 CH.sub.2 --                                                                     H         --CH.sub.2 F                                                                        N                                             953                                                                               o-Br CF.sub.3 CH.sub.2 --                                                                     H         --CH.sub.2 F                                                                        N                                             954                                                                               m-Br CF.sub.3 CH.sub.2 --                                                                     H         --CH.sub.2 F                                                                        N                                             955                                                                               p-Br CF.sub.3 CH.sub.2 --                                                                     H         --CH.sub.2 F                                                                        N                                             956                                                                               o-NH.sub.2                                                                          CF.sub.3 CH.sub.2 --                                                                     H         --CH.sub.2 F                                                                        N                                             957                                                                               m-NH.sub.2                                                                          CF.sub.3 CH.sub.2 --                                                                     H         --CH.sub.2 F                                                                        N                                             958                                                                               p-NH.sub.2                                                                          CF.sub.3 CH.sub.2 --                                                                     H         --CH.sub.2 F                                                                        N                                             959                                                                               o-NO.sub.2                                                                          CF.sub.3 CH.sub.2 --                                                                     H         --CH.sub.2 F                                                                        N                                             960                                                                               m-NO.sub.2                                                                          CF.sub.3 CH.sub.2 --                                                                     H         --CH.sub.2 F                                                                        N                                             961                                                                               p-NO.sub.2                                                                          CF.sub.3 CH.sub.2 --                                                                     H         --CH.sub.2 F                                                                        N                                             962                                                                               o-OC.sub.2 H.sub.5                                                                  CF.sub.3 CH.sub.2 --                                                                     H         --CH.sub.2 F                                                                        N                                             963                                                                               m-OC.sub.2 H.sub.5                                                                  CF.sub.3 CH.sub.2 --                                                                     H         --CH.sub.2 F                                                                        N                                             964                                                                               p-OC.sub.2 H.sub.5                                                                  CF.sub.3 CH.sub.2 --                                                                     H         --CH.sub.2 F                                                                        N                                             965                                                                               p-I  CF.sub.3 CH.sub.2 --                                                                     H         --CH.sub.2 F                                                                        N                                             966                                                                               o-O-n-Pr                                                                            CF.sub.3 CH.sub.2 --                                                                     H         --CH.sub.2 F                                                                        N                                             967                                                                               m-O-n-Pr                                                                            CF.sub.3 CH.sub.2 --                                                                     H         --CH.sub.2 F                                                                        N                                             968                                                                               p-O-n-Pr                                                                            CF.sub.3 CH.sub.2 --                                                                     H         --CH.sub.2 F                                                                        N                                             969                                                                               o-O-i-Pr                                                                            CF.sub.3 CH.sub.2 --                                                                     H         --CH.sub.2 F                                                                        N                                             970                                                                               m-O-i-Pr                                                                            CF.sub.3 CH.sub.2 --                                                                     H         --CH.sub.2 F                                                                        N                                             971                                                                               p-O-i-Pr                                                                            CF.sub.3 CH.sub.2 --                                                                     H         --CH.sub.2 F                                                                        N                                             972                                                                               o-O-n-Bu                                                                            CF.sub.3 CH.sub.2 --                                                                     H         --CH.sub.2 F                                                                        N                                             973                                                                               m-O-n-Bu                                                                            CF.sub.3 CH.sub.2 --                                                                     H         --CH.sub.2 F                                                                        N                                             974                                                                               p-O-n-Bu                                                                            CF.sub.3 CH.sub.2 --                                                                     H         --CH.sub.2 F                                                                        N                                             975                                                                               o-O-i-Bu                                                                            CF.sub.3 CH.sub.2 --                                                                     H         --CH.sub.2 F                                                                        N                                             976                                                                               m-O-i-Bu                                                                            CF.sub.3 CH.sub.2 --                                                                     H         --CH.sub.2 F                                                                        N                                             977                                                                               p-O-i-Bu                                                                            CF.sub.3 CH.sub.2 --                                                                     H         --CH.sub.2 F                                                                        N                                             978                                                                               o-OCF.sub.3                                                                         CF.sub.3 CH.sub.2 --                                                                     H         --CH.sub.2 F                                                                        N                                             979                                                                               m-OCF.sub.3                                                                         CF.sub.3 CH.sub.2 --                                                                     H         --CH.sub.2 F                                                                        N                                             980                                                                               p-OCF.sub.3                                                                         CF.sub.3 CH.sub.2 --                                                                     H         --CH.sub.2 F                                                                        N                                             981                                                                               H    H         H         --CH.sub.2 F                                                                        C                                             982                                                                               o-OCH.sub.3                                                                         H         H         --CH.sub.2 F                                                                        C                                             983                                                                               m-OCH.sub.3                                                                         H         H         --CH.sub.2 F                                                                        C                                             984                                                                               p-OCH.sub.3                                                                         H         H         --CH.sub.2 F                                                                        C                                             985                                                                               o-Cl H         H         --CH.sub.2 F                                                                        C                                             986                                                                               m-Cl H         H         --CH.sub.2 F                                                                        C                                             987                                                                               p-Cl H         H         --CH.sub.2 F                                                                        C                                             988                                                                               o-Br H         H         --CH.sub.2 F                                                                        C                                             989                                                                               m-Br H         H         --CH.sub.2 F                                                                        C                                             990                                                                               p-Br H         H         --CH.sub.2 F                                                                        C                                             991                                                                               o-NH.sub.2                                                                          H         H         --CH.sub.2 F                                                                        C                                             992                                                                               m-NH.sub.2                                                                          H         H         --CH.sub.2 F                                                                        C                                             993                                                                               p-NH.sub.2                                                                          H         H         --CH.sub.2 F                                                                        C                                             994                                                                               o-NO.sub.2                                                                          H         H         --CH.sub.2 F                                                                        C                                             995                                                                               m-NO.sub.2                                                                          H         H         --CH.sub.2 F                                                                        C                                             996                                                                               p-NO.sub.2                                                                          H         H         --CH.sub.2 F                                                                        C                                             997                                                                               o-OC.sub.2 H.sub.5                                                                  H         H         --CH.sub.2 F                                                                        C                                             998                                                                               m-OC.sub.2 H.sub.5                                                                  H         H         --CH.sub.2 F                                                                        C                                             999                                                                               p-OC.sub.2 H.sub.5                                                                  H         H         --CH.sub.2 F                                                                        C                                            1000                                                                               p-I  H         H         --CH.sub.2 F                                                                        C                                            1001                                                                               o-O-n-Pr                                                                            H         H         --CH.sub.2 F                                                                        C                                            1002                                                                               m-O-n-Pr                                                                            H         H         --CH.sub.2 F                                                                        C                                            1003                                                                               p-O-n-Pr                                                                            H         H         --CH.sub.2 F                                                                        C                                            1004                                                                               o-O-i-Pr                                                                            H         H         --CH.sub.2 F                                                                        C                                            1005                                                                               m-O-i-Pr                                                                            H         H         --CH.sub.2 F                                                                        C                                            1006                                                                               p-O-i-Pr                                                                            H         H         --CH.sub.2 F                                                                        C                                            1007                                                                               o-O-n-Bu                                                                            H         H         --CH.sub.2 F                                                                        C                                            1008                                                                               m-O-n-Bu                                                                            H         H         --CH.sub.2 F                                                                        C                                            1009                                                                               p-O-n-Bu                                                                            H         H         --CH.sub.2 F                                                                        C                                            1010                                                                               o-O-i-Bu                                                                            H         H         --CH.sub.2 F                                                                        C                                            1011                                                                               m-O-i-Bu                                                                            H         H         --CH.sub.2 F                                                                        C                                            1012                                                                               p-O-i-Bu                                                                            H         H         --CH.sub.2 F                                                                        C                                            1013                                                                               o-OCF.sub.3                                                                         H         H         --CH.sub.2 F                                                                        C                                            1014                                                                               m-OCF.sub.3                                                                         H         H         --CH.sub.2 F                                                                        C                                            1015                                                                               p-OCF.sub.3                                                                         H         H         --CH.sub.2 F                                                                        C                                            1016                                                                               H    H         H         --CH.sub.2 F                                                                        N                                            1017                                                                               o-OCH.sub.3                                                                         H         H         --CH.sub.2 F                                                                        N                                            1018                                                                               m-OCH.sub.3                                                                         H         H         --CH.sub.2 F                                                                        N                                            1019                                                                               p-OCH.sub.3                                                                         H         H         --CH.sub.2 F                                                                        N                                            1020                                                                               o-Cl H         H         --CH.sub.2 F                                                                        N                                            1021                                                                               m-Cl H         H         --CH.sub.2 F                                                                        N                                            1022                                                                               p-Cl H         H         --CH.sub.2 F                                                                        N                                            1023                                                                               o-Br H         H         --CH.sub.2 F                                                                        N                                            1024                                                                               m-Br H         H         --CH.sub.2 F                                                                        N                                            1025                                                                               p-Br H         H         --CH.sub.2 F                                                                        N                                            1026                                                                               o-NH.sub.2                                                                          H         H         --CH.sub.2 F                                                                        N                                            1027                                                                               m-NH.sub.2                                                                          H         H         --CH.sub.2 F                                                                        N                                            1028                                                                               p-NH.sub.2                                                                          H         H         --CH.sub.2 F                                                                        N                                            1029                                                                               o-NO.sub.2                                                                          H         H         --CH.sub.2 F                                                                        N                                            1030                                                                               m-NO.sub.2                                                                          H         H         --CH.sub.2 F                                                                        N                                            1031                                                                               p-NO.sub.2                                                                          H         H         --CH.sub.2 F                                                                        N                                            1032                                                                               o-OC.sub.2 H.sub.5                                                                  H         H         --CH.sub.2 F                                                                        N                                            1033                                                                               m-OC.sub.2 H.sub.5                                                                  H         H         --CH.sub.2 F                                                                        N                                            1034                                                                               p-OC.sub.2 H.sub.5                                                                  H         H         --CH.sub.2 F                                                                        N                                            1035                                                                               p-I  H         H         --CH.sub.2 F                                                                        N                                            1036                                                                               o-O-n-Pr                                                                            H         H         --CH.sub.2 F                                                                        N                                            1037                                                                               m-O-n-Pr                                                                            H         H         --CH.sub.2 F                                                                        N                                            1038                                                                               p-O-n-Pr                                                                            H         H         --CH.sub.2 F                                                                        N                                            1039                                                                               o-O-i-Pr                                                                            H         H         --CH.sub.2 F                                                                        N                                            1040                                                                               m-O-i-Pr                                                                            H         H         --CH.sub.2 F                                                                        N                                            1041                                                                               p-O-i-Pr                                                                            H         H         --CH.sub.2 F                                                                        N                                            1042                                                                               o-O-n-Bu                                                                            H         H         --CH.sub.2 F                                                                        N                                            1043                                                                               m-O-n-Bu                                                                            H         H         --CH.sub.2 F                                                                        N                                            1044                                                                               p-O-n-Bu                                                                            H         H         --CH.sub.2 F                                                                        N                                            1045                                                                               o-O-i-Bu                                                                            H         H         --CH.sub.2 F                                                                        N                                            1046                                                                               m-O-i-Bu                                                                            H         H         --CH.sub.2 F                                                                        N                                            1047                                                                               p-O-i-Bu                                                                            H         H         --CH.sub.2 F                                                                        N                                            1048                                                                               o-OCF.sub.3                                                                         H         H         --CH.sub.2 F                                                                        N                                            1049                                                                               m-OCF.sub.3                                                                         H         H         --CH.sub.2 F                                                                        N                                            1050                                                                               p-OCF.sub.3                                                                         H         H         --CH.sub.2 F                                                                        N                                            1051                                                                               H    CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     --CH.sub.2 OH                                                                       C                                            1052                                                                               o-OCH.sub.3                                                                         CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     --CH.sub.2 OH                                                                       C                                            1053                                                                               m-OCH.sub.3                                                                         CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     --CH.sub.2 OH                                                                       C                                            1054                                                                               p-OCH.sub.3                                                                         CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     --CH.sub.2 OH                                                                       C                                            1055                                                                               o-Cl CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     --CH.sub.2 OH                                                                       C                                            1056                                                                               m-Cl CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     --CH.sub.2 OH                                                                       C                                            1057                                                                               p-Cl CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     --CH.sub.2 OH                                                                       C                                            1058                                                                               o-Br CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     --CH.sub.2 OH                                                                       C                                            1059                                                                               m-Br CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     --CH.sub.2 OH                                                                       C                                            1060                                                                               p-Br CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     --CH.sub.2 OH                                                                       C                                            1061                                                                               o-NH.sub.2                                                                          CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     --CH.sub.2 OH                                                                       C                                            1062                                                                               m-NH.sub.2                                                                          CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     --CH.sub.2 OH                                                                       C                                            1063                                                                               p-NH.sub.2                                                                          CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     --CH.sub.2 OH                                                                       C                                            1064                                                                               o-NO.sub.2                                                                          CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     --CH.sub.2 OH                                                                       C                                            1065                                                                               m-NO.sub.2                                                                          CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     --CH.sub.2 OH                                                                       C                                            1066                                                                               p-NO.sub.2                                                                          CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     --CH.sub.2 OH                                                                       C                                            1067                                                                               o-OC.sub.2 H.sub.5                                                                  CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     --CH.sub.2 OH                                                                       C                                            1068                                                                               m-OC.sub.2 H.sub.5                                                                  CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     --CH.sub.2 OH                                                                       C                                            1069                                                                               p-OC.sub.2 H.sub.5                                                                  CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     --CH.sub.2 OH                                                                       C                                            1070                                                                               p-I  CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     --CH.sub.2 OH                                                                       C                                            1071                                                                               o-O-n-Pr                                                                            CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     --CH.sub.2 OH                                                                       C                                            1072                                                                               m-O-n-Pr                                                                            CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     --CH.sub.2 OH                                                                       C                                            1073                                                                               p-O-n-Pr                                                                            CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     --CH.sub.2 OH                                                                       C                                            1074                                                                               o-O-i-Pr                                                                            CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     --CH.sub.2 OH                                                                       C                                            1075                                                                               m-O-i-Pr                                                                            CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     --CH.sub.2 OH                                                                       C                                            1076                                                                               p-O-i-Pr                                                                            CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     --CH.sub.2 OH                                                                       C                                            1077                                                                               o-O-n-Bu                                                                            CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     --CH.sub.2 OH                                                                       C                                            1078                                                                               m-O-n-Bu                                                                            CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     --CH.sub.2 OH                                                                       C                                            1079                                                                               p-O-n-Bu                                                                            CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     --CH.sub.2 OH                                                                       C                                            1080                                                                               o-O-i-Bu                                                                            CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     --CH.sub.2 OH                                                                       C                                            1081                                                                               m-O-i-Bu                                                                            CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     --CH.sub.2 OH                                                                       C                                            1082                                                                               p-O-i-Bu                                                                            CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     --CH.sub.2 OH                                                                       C                                            1083                                                                               o-OCF.sub.3                                                                         CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     --CH.sub.2 OH                                                                       C                                            1084                                                                               m-OCF.sub.3                                                                         CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     --CH.sub.2 OH                                                                       C                                            1085                                                                               p-OCF.sub.3                                                                         CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     --CH.sub.2 OH                                                                       C                                            1086                                                                               H    CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     --CH.sub.2 OH                                                                       N                                            1087                                                                               o-OCH.sub.3                                                                         CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     --CH.sub.2 OH                                                                       N                                            1088                                                                               m-OCH.sub.3                                                                         CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     --CH.sub.2 OH                                                                       N                                            1089                                                                               p-OCH.sub.3                                                                         CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     --CH.sub.2 OH                                                                       N                                            1090                                                                               o-Cl CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     --CH.sub.2 OH                                                                       N                                            1091                                                                               m-Cl CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     --CH.sub.2 OH                                                                       N                                            1092                                                                               p-Cl CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     --CH.sub.2 OH                                                                       N                                            1093                                                                               o-Br CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     --CH.sub.2 OH                                                                       N                                            1094                                                                               m-Br CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     --CH.sub.2 OH                                                                       N                                            1095                                                                               p-Br CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     --CH.sub.2 OH                                                                       N                                            1096                                                                               o-NH.sub.2                                                                          CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     --CH.sub.2 OH                                                                       N                                            1097                                                                               m-NH.sub.2                                                                          CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     --CH.sub.2 OH                                                                       N                                            1098                                                                               p-NH.sub.2                                                                          CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     --CH.sub.2 OH                                                                       N                                            1099                                                                               o-NO.sub.2                                                                          CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     --CH.sub.2 OH                                                                       N                                            1100                                                                               m-NO.sub.2                                                                          CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     --CH.sub.2 OH                                                                       N                                            1101                                                                               p-NO.sub.2                                                                          CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     --CH.sub.2 OH                                                                       N                                            1102                                                                               o-OC.sub.2 H.sub.5                                                                  CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     --CH.sub.2 OH                                                                       N                                            1103                                                                               m-OC.sub.2 H.sub.5                                                                  CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     --CH.sub.2 OH                                                                       N                                            1104                                                                               p-OC.sub.2 H.sub.5                                                                  CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     --CH.sub.2 OH                                                                       N                                            1105                                                                               p-I  CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     --CH.sub.2 OH                                                                       N                                            1106                                                                               o-O-n-Pr                                                                            CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     --CH.sub.2 OH                                                                       N                                            1107                                                                               m-O-n-Pr                                                                            CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     --CH.sub.2 OH                                                                       N                                            1108                                                                               p-O-n-Pr                                                                            CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     --CH.sub.2 OH                                                                       N                                            1109                                                                               o-O-i-Pr                                                                            CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     --CH.sub.2 OH                                                                       N                                            1110                                                                               m-O-i-Pr                                                                            CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     --CH.sub.2 OH                                                                       N                                            1111                                                                               p-O-i-Pr                                                                            CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     --CH.sub.2 OH                                                                       N                                            1112                                                                               o-O-n-Bu                                                                            CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     --CH.sub.2 OH                                                                       N                                            1113                                                                               m-O-n-Bu                                                                            CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     --CH.sub.2 OH                                                                       N                                            1114                                                                               p-O-n-Bu                                                                            CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     --CH.sub.2 OH                                                                       N                                            1115                                                                               o-O-i-Bu                                                                            CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     --CH.sub.2 OH                                                                       N                                            1116                                                                               m-O-i-Bu                                                                            CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     --CH.sub.2 OH                                                                       N                                            1117                                                                               p-O-i-Bu                                                                            CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     --CH.sub.2 OH                                                                       N                                            1118                                                                               o-OCF.sub.3                                                                         CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     --CH.sub.2 OH                                                                       N                                            1119                                                                               m-OCF.sub.3                                                                         CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     --CH.sub.2 OH                                                                       N                                            1120                                                                               p-OCF.sub.3                                                                         CF.sub.3 CH.sub.2 --                                                                     CF.sub.3 CH.sub.2 --                                                                     --CH.sub.2 OH                                                                       N                                            1121                                                                               H    CF.sub.3 CH.sub.2 --                                                                     Me--      --CH.sub.2 OH                                                                       C                                            1122                                                                               o-OCH.sub.3                                                                         CF.sub.3 CH.sub.2 --                                                                     Me--      --CH.sub.2 OH                                                                       C                                            1123                                                                               m-OCH.sub.3                                                                         CF.sub.3 CH.sub.2 --                                                                     Me--      --CH.sub.2 OH                                                                       C                                            1124                                                                               p-OCH.sub.3                                                                         CF.sub.3 CH.sub.2 --                                                                     Me--      --CH.sub.2 OH                                                                       C                                            1125                                                                               o-Cl CF.sub.3 CH.sub.2 --                                                                     Me--      --CH.sub.2 OH                                                                       C                                            1126                                                                               m-Cl CF.sub.3 CH.sub.2 --                                                                     Me--      --CH.sub.2 OH                                                                       C                                            1127                                                                               p-Cl CF.sub.3 CH.sub.2 --                                                                     Me--      --CH.sub.2 OH                                                                       C                                            1128                                                                               o-Br CF.sub.3 CH.sub.2 --                                                                     Me--      --CH.sub.2 OH                                                                       C                                            1129                                                                               m-Br CF.sub.3 CH.sub.2 --                                                                     Me--      --CH.sub.2 OH                                                                       C                                            1130                                                                               p-Br CF.sub.3 CH.sub.2 --                                                                     Me--      --CH.sub.2 OH                                                                       C                                            1131                                                                               o-NH.sub.2                                                                          CF.sub.3 CH.sub.2 --                                                                     Me--      --CH.sub.2 OH                                                                       C                                            1132                                                                               m-NH.sub.2                                                                          CF.sub.3 CH.sub.2 --                                                                     Me--      --CH.sub.2 OH                                                                       C                                            1133                                                                               p-NH.sub.2                                                                          CF.sub.3 CH.sub.2 --                                                                     Me--      --CH.sub.2 OH                                                                       C                                            1134                                                                               o-NO.sub.2                                                                          CF.sub.3 CH.sub.2 --                                                                     Me--      --CH.sub.2 OH                                                                       C                                            1135                                                                               m-NO.sub.2                                                                          CF.sub.3 CH.sub.2 --                                                                     Me--      --CH.sub.2 OH                                                                       C                                            1136                                                                               p-NO.sub.2                                                                          CF.sub.3 CH.sub.2 --                                                                     Me--      --CH.sub.2 OH                                                                       C                                            1137                                                                               o-OC.sub.2 H.sub.5                                                                  CF.sub.3 CH.sub.2 --                                                                     Me--      --CH.sub.2 OH                                                                       C                                            1138                                                                               m-OC.sub.2 H.sub.5                                                                  CF.sub.3 CH.sub.2 --                                                                     Me--      --CH.sub.2 OH                                                                       C                                            1139                                                                               p-OC.sub.2 H.sub.5                                                                  CF.sub.3 CH.sub.2 --                                                                     Me--      --CH.sub.2 OH                                                                       C                                            1140                                                                               p-I  CF.sub.3 CH.sub.2 --                                                                     Me--      --CH.sub.2 OH                                                                       C                                            1141                                                                               o-O-n-Pr                                                                            CF.sub.3 CH.sub.2 --                                                                     Me--      --CH.sub.2 OH                                                                       C                                            1142                                                                               m-O-n-Pr                                                                            CF.sub.3 CH.sub.2 --                                                                     Me--      --CH.sub.2 OH                                                                       C                                            1143                                                                               p-O-n-Pr                                                                            CF.sub.3 CH.sub.2 --                                                                     Me--      --CH.sub.2 OH                                                                       C                                            1144                                                                               o-O-i-Pr                                                                            CF.sub.3 CH.sub.2 --                                                                     Me--      --CH.sub.2 OH                                                                       C                                            1145                                                                               m-O-i-Pr                                                                            CF.sub.3 CH.sub.2 --                                                                     Me--      --CH.sub.2 OH                                                                       C                                            1146                                                                               p-O-i-Pr                                                                            CF.sub.3 CH.sub.2 --                                                                     Me--      --CH.sub.2 OH                                                                       C                                            1147                                                                               o-O-n-Bu                                                                            CF.sub.3 CH.sub.2 --                                                                     Me--      --CH.sub.2 OH                                                                       C                                            1148                                                                               m-O-n-Bu                                                                            CF.sub.3 CH.sub.2 --                                                                     Me--      --CH.sub.2 OH                                                                       C                                            1149                                                                               p-O-n-Bu                                                                            CF.sub.3 CH.sub.2 --                                                                     Me--      --CH.sub.2 OH                                                                       C                                            1150                                                                               o-O-i-Bu                                                                            CF.sub.3 CH.sub.2 --                                                                     Me--      --CH.sub.2 OH                                                                       C                                            1151                                                                               m-O-i-Bu                                                                            CF.sub.3 CH.sub.2 --                                                                     Me--      --CH.sub.2 OH                                                                       C                                            1152                                                                               p-O-i-Bu                                                                            CF.sub.3 CH.sub.2 --                                                                     Me--      --CH.sub.2 OH                                                                       C                                            1153                                                                               o-OCF.sub.3                                                                         CF.sub.3 CH.sub.2 --                                                                     Me--      --CH.sub.2 OH                                                                       C                                            1154                                                                               m-OCF.sub.3                                                                         CF.sub.3 CH.sub.2 --                                                                     Me--      --CH.sub.2 OH                                                                       C                                            1155                                                                               p-OCF.sub.3                                                                         CF.sub.3 CH.sub.2 --                                                                     Me--      --CH.sub.2 OH                                                                       C                                            1156                                                                               H    CF.sub.3 CH.sub.2 --                                                                     Me--      --CH.sub.2 OH                                                                       N                                            1157                                                                               o-OCH.sub.3                                                                         CF.sub.3 CH.sub.2 --                                                                     Me--      --CH.sub.2 OH                                                                       N                                            1158                                                                               m-OCH.sub.3                                                                         CF.sub.3 CH.sub.2 --                                                                     Me--      --CH.sub.2 OH                                                                       N                                            1159                                                                               p-OCH.sub.3                                                                         CF.sub.3 CH.sub.2 --                                                                     Me--      --CH.sub.2 OH                                                                       N                                            1160                                                                               o-Cl CF.sub.3 CH.sub.2 --                                                                     Me--      --CH.sub.2 OH                                                                       N                                            1161                                                                               m-Cl CF.sub.3 CH.sub.2 --                                                                     Me--      --CH.sub.2 OH                                                                       N                                            1162                                                                               p-Cl CF.sub.3 CH.sub.2 --                                                                     Me--      --CH.sub.2 OH                                                                       N                                            1163                                                                               o-Br CF.sub.3 CH.sub.2 --                                                                     Me--      --CH.sub.2 OH                                                                       N                                            1164                                                                               m-Br CF.sub.3 CH.sub.2 --                                                                     Me--      --CH.sub.2 OH                                                                       N                                            1165                                                                               p-Br CF.sub.3 CH.sub.2 --                                                                     Me--      --CH.sub.2 OH                                                                       N                                            1166                                                                               o-NH.sub.2                                                                          CF.sub.3 CH.sub.2 --                                                                     Me--      --CH.sub.2 OH                                                                       N                                            1167                                                                               m-NH.sub.2                                                                          CF.sub.3 CH.sub.2 --                                                                     Me--      --CH.sub.2 OH                                                                       N                                            1168                                                                               p-NH.sub.2                                                                          CF.sub.3 CH.sub.2 --                                                                     Me--      --CH.sub.2 OH                                                                       N                                            1169                                                                               o-NO.sub.2                                                                          CF.sub.3 CH.sub.2 --                                                                     Me--      --CH.sub.2 OH                                                                       N                                            1170                                                                               m-NO.sub.2                                                                          CF.sub.3 CH.sub.2 --                                                                     Me--      --CH.sub.2 OH                                                                       N                                            1171                                                                               p-NO.sub.2                                                                          CF.sub.3 CH.sub.2 --                                                                     Me--      --CH.sub.2 OH                                                                       N                                            1172                                                                               o-OC.sub.2 H.sub.5                                                                  CF.sub.3 CH.sub.2 --                                                                     Me--      --CH.sub.2 OH                                                                       N                                            1173                                                                               m-OC.sub.2 H.sub.5                                                                  CF.sub.3 CH.sub.2 --                                                                     Me--      --CH.sub.2 OH                                                                       N                                            1174                                                                               p-OC.sub.2 H.sub.5                                                                  CF.sub.3 CH.sub.2 --                                                                     Me--      --CH.sub.2 OH                                                                       N                                            1175                                                                               p-I  CF.sub.3 CH.sub.2 --                                                                     Me--      --CH.sub.2 OH                                                                       N                                            1176                                                                               o-O-n-Pr                                                                            CF.sub.3 CH.sub.2 --                                                                     Me--      --CH.sub.2 OH                                                                       N                                            1177                                                                               m-O-n-Pr                                                                            CF.sub.3 CH.sub.2 --                                                                     Me--      --CH.sub.2 OH                                                                       N                                            1178                                                                               p-O-n-Pr                                                                            CF.sub.3 CH.sub.2 --                                                                     Me--      --CH.sub.2 OH                                                                       N                                            1179                                                                               o-O-i-Pr                                                                            CF.sub.3 CH.sub.2 --                                                                     Me--      --CH.sub.2 OH                                                                       N                                            1180                                                                               m-O-i-Pr                                                                            CF.sub.3 CH.sub.2 --                                                                     Me--      --CH.sub.2 OH                                                                       N                                            1181                                                                               p-O-i-Pr                                                                            CF.sub.3 CH.sub.2 --                                                                     Me--      --CH.sub.2 OH                                                                       N                                            1182                                                                               o-O-n-Bu                                                                            CF.sub.3 CH.sub.2 --                                                                     Me--      --CH.sub.2 OH                                                                       N                                            1183                                                                               m-O-n-Bu                                                                            CF.sub.3 CH.sub.2 --                                                                     Me--      --CH.sub.2 OH                                                                       N                                            1184                                                                               p-O-n-Bu                                                                            CF.sub.3 CH.sub.2 --                                                                     Me--      --CH.sub.2 OH                                                                       N                                            1185                                                                               o-O-i-Bu                                                                            CF.sub.3 CH.sub.2 --                                                                     Me--      --CH.sub.2 OH                                                                       N                                            1186                                                                               m-O-i-Bu                                                                            CF.sub.3 CH.sub.2 --                                                                     Me--      --CH.sub.2 OH                                                                       N                                            1187                                                                               p-O-i-Bu                                                                            CF.sub.3 CH.sub.2 --                                                                     Me--      --CH.sub.2 OH                                                                       N                                            1188                                                                               o-OCF.sub.3                                                                         CF.sub.3 CH.sub.2 --                                                                     Me--      --CH.sub.2 OH                                                                       N                                            1189                                                                               m-OCF.sub.3                                                                         CF.sub.3 CH.sub.2 --                                                                     Me--      --CH.sub.2 OH                                                                       N                                            1190                                                                               p-OCF.sub.3                                                                         CF.sub.3 CH.sub.2 --                                                                     Me--      --CH.sub.2 OH                                                                       N                                            1191                                                                               H    CF.sub.3 CH.sub.2 --                                                                     Et--      --CH.sub.2 OH                                                                       C                                            1192                                                                               o-OCH.sub.3                                                                         CF.sub.3 CH.sub.2 --                                                                     Et--      --CH.sub.2 OH                                                                       C                                            1193                                                                               m-OCH.sub.3                                                                         CF.sub.3 CH.sub.2 --                                                                     Et--      --CH.sub.2 OH                                                                       C                                            1194                                                                               p-OCH.sub.3                                                                         CF.sub.3 CH.sub.2 --                                                                     Et--      --CH.sub.2 OH                                                                       C                                            1195                                                                               o-Cl CF.sub.3 CH.sub.2 --                                                                     Et--      --CH.sub.2 OH                                                                       C                                            1196                                                                               m-Cl CF.sub.3 CH.sub.2 --                                                                     Et--      --CH.sub.2 OH                                                                       C                                            1197                                                                               p-Cl CF.sub.3 CH.sub.2 --                                                                     Et--      --CH.sub.2 OH                                                                       C                                            1198                                                                               o-Br CF.sub.3 CH.sub.2 --                                                                     Et--      --CH.sub.2 OH                                                                       C                                            1199                                                                               m-Br CF.sub.3 CH.sub.2 --                                                                     Et--      --CH.sub.2 OH                                                                       C                                            1200                                                                               p-Br CF.sub.3 CH.sub.2 --                                                                     Et--      --CH.sub.2 OH                                                                       C                                            1201                                                                               o-NH.sub.2                                                                          CF.sub.3 CH.sub.2 --                                                                     Et--      --CH.sub.2 OH                                                                       C                                            1202                                                                               m-NH.sub.2                                                                          CF.sub.3 CH.sub.2 --                                                                     Et--      --CH.sub.2 OH                                                                       C                                            1203                                                                               p-NH.sub.2                                                                          CF.sub.3 CH.sub.2 --                                                                     Et--      --CH.sub.2 OH                                                                       C                                            1204                                                                               o-NO.sub.2                                                                          CF.sub.3 CH.sub.2 --                                                                     Et--      --CH.sub.2 OH                                                                       C                                            1205                                                                               m-NO.sub.2                                                                          CF.sub.3 CH.sub.2 --                                                                     Et--      --CH.sub.2 OH                                                                       C                                            1206                                                                               p-NO.sub.2                                                                          CF.sub.3 CH.sub.2 --                                                                     Et--      --CH.sub.2 OH                                                                       C                                            1207                                                                               o-OC.sub.2 H.sub.5                                                                  CF.sub.3 CH.sub.2 --                                                                     Et--      --CH.sub.2 OH                                                                       C                                            1208                                                                               m-OC.sub.2 H.sub.5                                                                  CF.sub.3 CH.sub.2 --                                                                     Et--      --CH.sub.2 OH                                                                       C                                            1209                                                                               p-OC.sub.2 H.sub.5                                                                  CF.sub.3 CH.sub.2 --                                                                     Et--      --CH.sub.2 OH                                                                       C                                            1210                                                                               p-I  CF.sub.3 CH.sub.2 --                                                                     Et--      --CH.sub.2 OH                                                                       C                                            1211                                                                               o-O-n-Pr                                                                            CF.sub.3 CH.sub.2 --                                                                     Et--      --CH.sub.2 OH                                                                       C                                            1212                                                                               m-O-n-Pr                                                                            CF.sub.3 CH.sub.2 --                                                                     Et--      --CH.sub.2 OH                                                                       C                                            1213                                                                               p-O-n-Pr                                                                            CF.sub.3 CH.sub.2 --                                                                     Et--      --CH.sub.2 OH                                                                       C                                            1214                                                                               o-O-i-Pr                                                                            CF.sub.3 CH.sub.2 --                                                                     Et--      --CH.sub.2 OH                                                                       C                                            1215                                                                               m-O-i-Pr                                                                            CF.sub.3 CH.sub.2 --                                                                     Et--      --CH.sub.2 OH                                                                       C                                            1216                                                                               p-O-i-Pr                                                                            CF.sub.3 CH.sub.2 --                                                                     Et--      --CH.sub.2 OH                                                                       C                                            1217                                                                               o-O-n-Bu                                                                            CF.sub.3 CH.sub.2 --                                                                     Et--      --CH.sub.2 OH                                                                       C                                            1218                                                                               m-O-n-Bu                                                                            CF.sub.3 CH.sub.2 --                                                                     Et--      --CH.sub.2 OH                                                                       C                                            1219                                                                               p-O-n-Bu                                                                            CF.sub.3 CH.sub.2 --                                                                     Et--      --CH.sub.2 OH                                                                       C                                            1220                                                                               o-O-i-Bu                                                                            CF.sub.3 CH.sub.2 --                                                                     Et--      --CH.sub.2 OH                                                                       C                                            1221                                                                               m-O-i-Bu                                                                            CF.sub.3 CH.sub.2 --                                                                     Et--      --CH.sub.2 OH                                                                       C                                            1222                                                                               p-O-i-Bu                                                                            CF.sub.3 CH.sub.2 --                                                                     Et--      --CH.sub.2 OH                                                                       C                                            1223                                                                               o-OCF.sub.3                                                                         CF.sub.3 CH.sub.2 --                                                                     Et--      --CH.sub.2 OH                                                                       C                                            1224                                                                               m-OCF.sub.3                                                                         CF.sub.3 CH.sub.2 --                                                                     Et--      --CH.sub.2 OH                                                                       C                                            1225                                                                               p-OCF.sub.3                                                                         CF.sub.3 CH.sub.2 --                                                                     Et--      --CH.sub.2 OH                                                                       C                                            1226                                                                               H    CF.sub.3 CH.sub.2 --                                                                     Et--      --CH.sub.2 OH                                                                       N                                            1227                                                                               o-OCH.sub.3                                                                         CF.sub.3 CH.sub.2 --                                                                     Et--      --CH.sub.2 OH                                                                       N                                            1228                                                                               m-OCH.sub.3                                                                         CF.sub.3 CH.sub.2 --                                                                     Et--      --CH.sub.2 OH                                                                       N                                            1229                                                                               p-OCH.sub.3                                                                         CF.sub.3 CH.sub.2 --                                                                     Et--      --CH.sub.2 OH                                                                       N                                            1230                                                                               o-Cl CF.sub.3 CH.sub.2 --                                                                     Et--      --CH.sub.2 OH                                                                       N                                            1231                                                                               m-Cl CF.sub.3 CH.sub.2 --                                                                     Et--      --CH.sub.2 OH                                                                       N                                            1232                                                                               p-Cl CF.sub.3 CH.sub.2 --                                                                     Et--      --CH.sub.2 OH                                                                       N                                            1233                                                                               o-Br CF.sub.3 CH.sub.2 --                                                                     Et--      --CH.sub.2 OH                                                                       N                                            1234                                                                               m-Br CF.sub.3 CH.sub.2 --                                                                     Et--      --CH.sub.2 OH                                                                       N                                            1235                                                                               p-Br CF.sub.3 CH.sub.2 --                                                                     Et--      --CH.sub.2 OH                                                                       N                                            1236                                                                               o-NH.sub.2                                                                          CF.sub.3 CH.sub.2 --                                                                     Et--      --CH.sub.2 OH                                                                       N                                            1237                                                                               m-NH.sub.2                                                                          CF.sub.3 CH.sub.2 --                                                                     Et--      --CH.sub.2 OH                                                                       N                                            1238                                                                               p-NH.sub.2                                                                          CF.sub.3 CH.sub.2 --                                                                     Et--      --CH.sub.2 OH                                                                       N                                            1239                                                                               o-NO.sub.2                                                                          CF.sub.3 CH.sub.2 --                                                                     Et--      --CH.sub.2 OH                                                                       N                                            1240                                                                               m-NO.sub.2                                                                          CF.sub.3 CH.sub.2 --                                                                     Et--      --CH.sub.2 OH                                                                       N                                            1241                                                                               p-NO.sub.2                                                                          CF.sub.3 CH.sub.2 --                                                                     Et--      --CH.sub.2 OH                                                                       N                                            1242                                                                               o-OC.sub.2 H.sub.5                                                                  CF.sub.3 CH.sub.2 --                                                                     Et--      --CH.sub.2 OH                                                                       N                                            1243                                                                               m-OC.sub.2 H.sub.5                                                                  CF.sub.3 CH.sub.2 --                                                                     Et--      --CH.sub.2 OH                                                                       N                                            1244                                                                               p-OC.sub.2 H.sub.5                                                                  CF.sub.3 CH.sub.2 --                                                                     Et--      --CH.sub.2 OH                                                                       N                                            1245                                                                               p-I  CF.sub.3 CH.sub.2 --                                                                     Et--      --CH.sub.2 OH                                                                       N                                            1246                                                                               o-O-n-Pr                                                                            CF.sub.3 CH.sub.2 --                                                                     Et--      --CH.sub.2 OH                                                                       N                                            1247                                                                               m-O-n-Pr                                                                            CF.sub.3 CH.sub.2 --                                                                     Et--      --CH.sub.2 OH                                                                       N                                            1248                                                                               p-O-n-Pr                                                                            CF.sub.3 CH.sub.2 --                                                                     Et--      --CH.sub.2 OH                                                                       N                                            1249                                                                               o-O-i-Pr                                                                            CF.sub.3 CH.sub.2 --                                                                     Et--      --CH.sub.2 OH                                                                       N                                            1250                                                                               m-O-i-Pr                                                                            CF.sub.3 CH.sub.2 --                                                                     Et--      --CH.sub.2 OH                                                                       N                                            1251                                                                               p-O-i-Pr                                                                            CF.sub.3 CH.sub.2 --                                                                     Et--      --CH.sub.2 OH                                                                       N                                            1252                                                                               o-O-n-Bu                                                                            CF.sub.3 CH.sub.2 --                                                                     Et--      --CH.sub.2 OH                                                                       N                                            1253                                                                               m-O-n-Bu                                                                            CF.sub.3 CH.sub.2 --                                                                     Et--      --CH.sub.2 OH                                                                       N                                            1254                                                                               p-O-n-Bu                                                                            CF.sub.3 CH.sub.2 --                                                                     Et--      --CH.sub.2 OH                                                                       N                                            1255                                                                               o-O-i-Bu                                                                            CF.sub.3 CH.sub.2 --                                                                     Et--      --CH.sub.2 OH                                                                       N                                            1256                                                                               m-C-i-Bu                                                                            CF.sub.3 CH.sub.2 --                                                                     Et--      --CH.sub.2 OH                                                                       N                                            1257                                                                               p-O-i-Bu                                                                            CF.sub.3 CH.sub.2 --                                                                     Et--      --CH.sub.2 OH                                                                       N                                            1258                                                                               o-OCF.sub.3                                                                         CF.sub.3 CH.sub.2 --                                                                     Et--      --CH.sub.2 OH                                                                       N                                            1259                                                                               m-OCF.sub.3                                                                         CF.sub.3 CH.sub.2 --                                                                     Et--      --CH.sub.2 OH                                                                       N                                            1260                                                                               p-OCF.sub.3                                                                         CF.sub.3 CH.sub.2 --                                                                     Et--      --CH.sub.2 OH                                                                       N                                            1261                                                                               H    CF.sub.3 CH.sub.2 --                                                                     H         --CH.sub.2 OH                                                                       C                                            1262                                                                               o-OCH.sub.3                                                                         CF.sub.3 CH.sub.2 --                                                                     H         --CH.sub.2 OH                                                                       C                                            1263                                                                               m-OCH.sub.3                                                                         CF.sub.3 CH.sub.2 --                                                                     H         --CH.sub.2 OH                                                                       C                                            1264                                                                               p-OCH.sub.3                                                                         CF.sub.3 CH.sub.2 --                                                                     H         --CH.sub.2 OH                                                                       C                                            1265                                                                               o-Cl CF.sub.3 CH.sub.2 --                                                                     H         --CH.sub.2 OH                                                                       C                                            1266                                                                               m-Cl CF.sub.3 CH.sub.2 --                                                                     H         --CH.sub.2 OH                                                                       C                                            1267                                                                               p-Cl CF.sub.3 CH.sub.2 --                                                                     H         --CH.sub.2 OH                                                                       C                                            1268                                                                               o-Br CF.sub.3 CH.sub.2 --                                                                     H         --CH.sub.2 OH                                                                       C                                            1269                                                                               m-Br CF.sub.3 CH.sub.2 --                                                                     H         --CH.sub.2 OH                                                                       C                                            1270                                                                               p-Br CF.sub.3 CH.sub.2 --                                                                     H         --CH.sub.2 OH                                                                       C                                            1271                                                                               o-NH.sub.2                                                                          CF.sub.3 CH.sub.2 --                                                                     H         --CH.sub.2 OH                                                                       C                                            1272                                                                               m-NH.sub.2                                                                          CF.sub.3 CH.sub.2 --                                                                     H         --CH.sub.2 OH                                                                       C                                            1273                                                                               p-NH.sub.2                                                                          CF.sub.3 CH.sub.2 --                                                                     H         --CH.sub.2 OH                                                                       C                                            1274                                                                               o-NO.sub.2                                                                          CF.sub.3 CH.sub.2 --                                                                     H         --CH.sub.2 OH                                                                       C                                            1275                                                                               m-NO.sub.2                                                                          CF.sub.3 CH.sub.2 --                                                                     H         --CH.sub.2 OH                                                                       C                                            1276                                                                               p-NO.sub.2                                                                          CF.sub.3 CH.sub.2 --                                                                     H         --CH.sub.2 OH                                                                       C                                            1277                                                                               o-OC.sub.2 H.sub.5                                                                  CF.sub.3 CH.sub.2 --                                                                     H         --CH.sub.2 OH                                                                       C                                            1278                                                                               m-OC.sub.2 H.sub.5                                                                  CF.sub.3 CH.sub.2 --                                                                     H         --CH.sub.2 OH                                                                       C                                            1279                                                                               p-OC.sub.2 H.sub.5                                                                  CF.sub.3 CH.sub.2 --                                                                     H         --CH.sub.2 OH                                                                       C                                            1280                                                                               p-I  CF.sub.3 CH.sub.2 --                                                                     H         --CH.sub.2 OH                                                                       C                                            1281                                                                               o-O-n-Pr                                                                            CF.sub.3 CH.sub.2 --                                                                     H         --CH.sub.2 OH                                                                       C                                            1282                                                                               m-O-n-Pr                                                                            CF.sub.3 CH.sub.2 --                                                                     H         --CH.sub.2 OH                                                                       C                                            1283                                                                               p-O-n-Pr                                                                            CF.sub.3 CH.sub.2 --                                                                     H         --CH.sub.2 OH                                                                       C                                            1284                                                                               o-O-i-Pr                                                                            CF.sub.3 CH.sub.2 --                                                                     H         --CH.sub.2 OH                                                                       C                                            1285                                                                               m-O-i-Pr                                                                            CF.sub.3 CH.sub.2 --                                                                     H         --CH.sub.2 OH                                                                       C                                            1286                                                                               p-O-i-Pr                                                                            CF.sub.3 CH.sub.2 --                                                                     H         --CH.sub.2 OH                                                                       C                                            1287                                                                               o-O-n-Bu                                                                            CF.sub.3 CH.sub.2 --                                                                     H         --CH.sub.2 OH                                                                       C                                            1288                                                                               m-O-n-Bu                                                                            CF.sub.3 CH.sub.2 --                                                                     H         --CH.sub.2 OH                                                                       C                                            1289                                                                               p-O-n-Bu                                                                            CF.sub.3 CH.sub.2 --                                                                     H         --CH.sub.2 OH                                                                       C                                            1290                                                                               o-O-i-Bu                                                                            CF.sub.3 CH.sub.2 --                                                                     H         --CH.sub.2 OH                                                                       C                                            1291                                                                               m-O-i-Bu                                                                            CF.sub.3 CH.sub.2 --                                                                     H         --CH.sub.2 OH                                                                       C                                            1292                                                                               p-O-i-Bu                                                                            CF.sub.3 CH.sub.2 --                                                                     H         --CH.sub.2 OH                                                                       C                                            1293                                                                               o-OCF.sub.3                                                                         CF.sub.3 CH.sub.2 --                                                                     H         --CH.sub.2 OH                                                                       C                                            1294                                                                               m-OCF.sub.3                                                                         CF.sub.3 CH.sub.2 --                                                                     H         --CH.sub.2 OH                                                                       C                                            1295                                                                               p-OCF.sub.3                                                                         CF.sub.3 CH.sub.2 --                                                                     H         --CH.sub.2 OH                                                                       C                                            1296                                                                               H    CF.sub.3 CH.sub.2 --                                                                     H         --CH.sub.2 OH                                                                       N                                            1297                                                                               o-OCH.sub.3                                                                         CF.sub.3 CH.sub.2 --                                                                     H         --CH.sub.2 OH                                                                       N                                            1298                                                                               m-OCH.sub.3                                                                         CF.sub.3 CH.sub.2 --                                                                     H         --CH.sub.2 OH                                                                       N                                            1299                                                                               p-OCH.sub.3                                                                         CF.sub.3 CH.sub.2 --                                                                     H         --CH.sub.2 OH                                                                       N                                            1300                                                                               o-Cl CF.sub.3 CH.sub.2 --                                                                     H         --CH.sub.2 OH                                                                       N                                            1301                                                                               m-Cl CF.sub.3 CH.sub.2 --                                                                     H         --CH.sub.2 OH                                                                       N                                            1302                                                                               p-Cl CF.sub.3 CH.sub.2 --                                                                     H         --CH.sub.2 dH                                                                       N                                            1303                                                                               o-Br CF.sub.3 CH.sub.2 --                                                                     H         --CH.sub.2 OH                                                                       N                                            1304                                                                               m-Br CF.sub.3 CH.sub.2 --                                                                     H         --CH.sub.2 OH                                                                       N                                            1305                                                                               p-Br CF.sub.3 CH.sub.2 --                                                                     H         --CH.sub.2 OH                                                                       N                                            1306                                                                               o-NH.sub.2                                                                          CF.sub.3 CH.sub.2 --                                                                     H         --CH.sub.2 OH                                                                       N                                            1307                                                                               m-NH.sub.2                                                                          CF.sub.3 CH.sub.2 --                                                                     H         --CH.sub.2 OH                                                                       N                                            1308                                                                               p-NH.sub.2                                                                          CF.sub.3 CH.sub.2 --                                                                     H         --CH.sub.2 OH                                                                       N                                            1309                                                                               o-NO.sub.2                                                                          CF.sub.3 CH.sub.2 --                                                                     H         --CH.sub.2 OH                                                                       N                                            1310                                                                               m-NO.sub.2                                                                          CF.sub.3 CH.sub.2 --                                                                     H         --CH.sub.2 OH                                                                       N                                            1311                                                                               p-NO.sub.2                                                                          CF.sub.3 CH.sub.2 --                                                                     H         --CH.sub.2 OH                                                                       N                                            1312                                                                               o-OC.sub.2 H.sub.5                                                                  CF.sub.3 CH.sub.2 --                                                                     H         --CH.sub.2 OH                                                                       N                                            1313                                                                               m-OC.sub.2 H.sub.5                                                                  CF.sub.3 CH.sub.2 --                                                                     H         --CH.sub.2 OH                                                                       N                                            1314                                                                               p-OC.sub.2 H.sub.5                                                                  CF.sub.3 CH.sub.2 --                                                                     H         --CH.sub.2 OH                                                                       N                                            1315                                                                               p-I  CF.sub.3 CH.sub.2 --                                                                     H         --CH.sub.2 OH                                                                       N                                            1316                                                                               o-O-n-Pr                                                                            CF.sub.3 CH.sub.2 --                                                                     H         --CH.sub.2 OH                                                                       N                                            1317                                                                               m-O-n-Pr                                                                            CF.sub.3 CH.sub.2 --                                                                     H         --CH.sub.2 OH                                                                       N                                            1318                                                                               p-O-n-Pr                                                                            CF.sub.3 CH.sub.2 --                                                                     H         --CH.sub.2 OH                                                                       N                                            1319                                                                               o-O-i-Pr                                                                            CF.sub.3 CH.sub.2 --                                                                     H         --CH.sub.2 OH                                                                       N                                            1320                                                                               m-O-i-Pr                                                                            CF.sub.3 CH.sub.2 --                                                                     H         --CH.sub.2 OH                                                                       N                                            1321                                                                               p-O-i-Pr                                                                            CF.sub.3 CH.sub.2 --                                                                     H         --CH.sub.2 OH                                                                       N                                            1322                                                                               o-O-n-Bu                                                                            CF.sub.3 CH.sub.2 --                                                                     H         --CH.sub.2 OH                                                                       N                                            1323                                                                               m-O-n-Bu                                                                            CF.sub.3 CH.sub.2 --                                                                     H         --CH.sub.2 OH                                                                       N                                            1324                                                                               p-O-n-Bu                                                                            CF.sub.3 CH.sub.2 --                                                                     H         --CH.sub.2 OH                                                                       N                                            1325                                                                               o-O-i-Bu                                                                            CF.sub.3 CH.sub.2 --                                                                     H         --CH.sub.2 OH                                                                       N                                            1326                                                                               m-O-i-Bu                                                                            CF.sub.3 CH.sub.2 --                                                                     H         --CH.sub.2 OH                                                                       N                                            1327                                                                               p-O-i-Bu                                                                            CF.sub.3 CH.sub.2 --                                                                     H         --CH.sub.2 OH                                                                       N                                            1328                                                                               o-OCF.sub.3                                                                         CF.sub.3 CH.sub.2 --                                                                     H         --CH.sub.2 OH                                                                       N                                            1329                                                                               m-OCF.sub.3                                                                         CF.sub.3 CH.sub.2 --                                                                     H         --CH.sub.2 OH                                                                       N                                            1330                                                                               p-OCF.sub.3                                                                         CF.sub.3 CH.sub.2 --                                                                     H         --CH.sub.2 OH                                                                       N                                            1331                                                                               H    H         H         --CH.sub.2 OH                                                                       C                                            1332                                                                               o-OCH.sub.3                                                                         H         H         --CH.sub.2 OH                                                                       C                                            1333                                                                               m-OCH.sub.3                                                                         H         H         --CH.sub.2 OH                                                                       C                                            1334                                                                               p-OCH.sub.3                                                                         H         H         --CH.sub.2 OH                                                                       C                                            1335                                                                               o-Cl H         H         --CH.sub.2 OH                                                                       C                                            1336                                                                               m-Cl H         H         --CH.sub.2 OH                                                                       C                                            1337                                                                               p-Cl H         H         --CH.sub.2 OH                                                                       C                                            1338                                                                               o-Br H         H         --CH.sub.2 OH                                                                       C                                            1339                                                                               m-Br H         H         --CH.sub.2 OH                                                                       C                                            1340                                                                               p-Br H         H         --CH.sub.2 OH                                                                       C                                            1341                                                                               o-NH.sub.2                                                                          H         H         --CH.sub.2 OH                                                                       C                                            1342                                                                               m-NH.sub.2                                                                          H         H         --CH.sub.2 OH                                                                       C                                            1343                                                                               p-NH.sub.2                                                                          H         H         --CH.sub.2 OH                                                                       C                                            1344                                                                               o-NO.sub.2                                                                          H         H         --CH.sub.2 OH                                                                       C                                            1345                                                                               m-NO.sub.2                                                                          H         H         --CH.sub.2 OH                                                                       C                                            1346                                                                               p-NO.sub.2                                                                          H         H         --CH.sub.2 OH                                                                       C                                            1347                                                                               o-OC.sub.2 H.sub.5                                                                  H         H         --CH.sub.2 OH                                                                       C                                            1348                                                                               m-OC.sub.2 H.sub.5                                                                  H         H         --CH.sub.2 OH                                                                       C                                            1349                                                                               p-OC.sub.2 H.sub.5                                                                  H         H         --CH.sub.2 OH                                                                       C                                            1350                                                                               p-I  H         H         --CH.sub.2 OH                                                                       C                                            1351                                                                               o-O-n-Pr                                                                            H         H         --CH.sub.2 OH                                                                       C                                            1352                                                                               m-O-n-Pr                                                                            H         H         --CH.sub.2 OH                                                                       C                                            1353                                                                               p-O-n-Pr                                                                            H         H         --CH.sub.2 OH                                                                       C                                            1354                                                                               o-O-i-Pr                                                                            H         H         --CH.sub.2 OH                                                                       C                                            1355                                                                               m-O-i-Pr                                                                            H         H         --CH.sub.2 OH                                                                       C                                            1356                                                                               p-O-i-Pr                                                                            H         H         --CH.sub.2 OH                                                                       C                                            1357                                                                               o-O-n-Bu                                                                            H         H         --CH.sub.2 OH                                                                       C                                            1358                                                                               m-O-n-Bu                                                                            H         H         --CH.sub.2 OH                                                                       C                                            1359                                                                               p-O-n-Bu                                                                            H         H         --CH.sub.2 OH                                                                       C                                            1360                                                                               o-O-i-Bu                                                                            H         H         --CH.sub.2 OH                                                                       C                                            1361                                                                               m-O-i-Bu                                                                            H         H         --CH.sub.2 OH                                                                       C                                            1362                                                                               p-O-i-Bu                                                                            H         H         --CH.sub.2 OH                                                                       C                                            1363                                                                               o-OCF.sub.3                                                                         H         H         --CH.sub.2 OH                                                                       C                                            1364                                                                               m-OCF.sub.3                                                                         H         H         --CH.sub.2 OH                                                                       C                                            1365                                                                               p-OCF.sub.3                                                                         H         H         --CH.sub.2 OH                                                                       C                                            1366                                                                               H    H         H         --CH.sub.2 OH                                                                       N                                            1367                                                                               o-OCH.sub.3                                                                         H         H         --CH.sub.2 OH                                                                       N                                            1368                                                                               m-OCH.sub.3                                                                         H         H         --CH.sub.2 OH                                                                       N                                            1369                                                                               p-OCH.sub.3                                                                         H         H         --CH.sub.2 OH                                                                       N                                            1370                                                                               o-Cl H         H         --CH.sub.2 OH                                                                       N                                            1371                                                                               m-Cl H         H         --CH.sub.2 OH                                                                       N                                            1372                                                                               p-Cl H         H         --CH.sub.2 OH                                                                       N                                            1373                                                                               o-Br H         H         --CH.sub.2 OH                                                                       N                                            1374                                                                               m-Br H         H         --CH.sub.2 OH                                                                       N                                            1375                                                                               p-Br H         H         --CH.sub.2 OH                                                                       N                                            1376                                                                               o-NH.sub.2                                                                          H         H         --CH.sub.2 OH                                                                       N                                            1377                                                                               m-NH.sub.2                                                                          H         H         --CH.sub.2 OH                                                                       N                                            1378                                                                               p-NH.sub.2                                                                          H         H         --CH.sub.2 OH                                                                       N                                            1379                                                                               o-NO.sub.2                                                                          H         H         --CH.sub.2 OH                                                                       N                                            1380                                                                               m-NO.sub.2                                                                          H         H         --CH.sub.2 OH                                                                       N                                            1381                                                                               p-NO.sub.2                                                                          H         H         --CH.sub.2 OH                                                                       N                                            1382                                                                               o-OC.sub.2 H.sub.5                                                                  H         H         --CH.sub.2 OH                                                                       N                                            1383                                                                               m-OC.sub.2 H.sub.5                                                                  H         H         --CH.sub.2 OH                                                                       N                                            1384                                                                               p-OC.sub.2 H.sub.5                                                                  H         H         --CH.sub.2 OH                                                                       N                                            1385                                                                               p-I  H         H         --CH.sub.2 OH                                                                       N                                            1386                                                                               o-O-n-Pr                                                                            H         H         --CH.sub.2 OH                                                                       N                                            1387                                                                               m-O-n-Pr                                                                            H         H         --CH.sub.2 OH                                                                       N                                            1388                                                                               p-O-n-Pr                                                                            H         H         --CH.sub.2 OH                                                                       N                                            1389                                                                               o-O-i-Pr                                                                            H         H         --CH.sub.2 OH                                                                       N                                            1390                                                                               m-O-i-Pr                                                                            H         H         --CH.sub.2 OH                                                                       N                                            1391                                                                               p-O-i-Pr                                                                            H         H         --CH.sub.2 OH                                                                       N                                            1392                                                                               o-O-n-Bu                                                                            H         H         --CH.sub.2 OH                                                                       N                                            1393                                                                               m-O-n-Bu                                                                            H         H         --CH.sub.2 OH                                                                       N                                            1394                                                                               p-O-n-Bu                                                                            H         H         --CH.sub.2 OH                                                                       N                                            1395                                                                               o-O-i-Bu                                                                            H         H         --CH.sub.2 OH                                                                       N                                            1396                                                                               m-O-i-Bu                                                                            H         H         --CH.sub.2 OH                                                                       N                                            1397                                                                               p-O-i-Bu                                                                            H         H         --CH.sub.2 OH                                                                       N                                            1398                                                                               o-OCF.sub.3                                                                         H         H         --CH.sub.2 OH                                                                       N                                            1399                                                                               m-OCF.sub.3                                                                         H         H         --CH.sub.2 OH                                                                       N                                            1400                                                                               p-OCF.sub.3                                                                         H         H         --CH.sub.2 OH                                                                       N                                            1401                                                                               H    --CH.sub.2 O--CO-t-Bu                                                                    --CH.sub.2 O--CO-t-Bu                                                                    H    C                                            1402                                                                               o-OCH.sub.3                                                                         --CH.sub.2 O--CO-t-Bu                                                                    --CH.sub.2 O--CO-t-Bu                                                                    H    C                                            1403                                                                               m-OCH.sub.3                                                                         --CH.sub.2 O--CO-t-Bu                                                                    --CH.sub.2 O--CO-t-Bu                                                                    H    C                                            1404                                                                               p-OCH.sub.3                                                                         --CH.sub.2 O--CO-t-Bu                                                                    --CH.sub.2 O--CO-t-Bu                                                                    H    C                                            1405                                                                               o-Cl --CH.sub.2 O--CO-t-Bu                                                                    --CH.sub.2 O--CO-t-Bu                                                                    H    C                                            1406                                                                               m-Cl --CH.sub.2 O--CO-t-Bu                                                                    --CH.sub.2 O--CO-t-Bu                                                                    H    C                                            1407                                                                               p-Cl --CH.sub.2 O--CO-t-Bu                                                                    --CH.sub.2 O--CO-t-Bu                                                                    H    C                                            1408                                                                               o-Br --CH.sub.2 O--CO-t-Bu                                                                    --CH.sub.2 O--CO-t-Bu                                                                    H    C                                            1409                                                                               m-Br --CH.sub.2 O--CO-t-Bu                                                                    --CH.sub.2 O--CO-t-Bu                                                                    H    C                                            1410                                                                               p-Br --CH.sub.2 O--CO-t-Bu                                                                    --CH.sub.2 O--CO-t-Bu                                                                    H    C                                            1411                                                                               o-NH.sub.2                                                                          --CH.sub.2 O--CO-t-Bu                                                                    --CH.sub.2 O--CO-t-Bu                                                                    H    C                                            1412                                                                               m-NH.sub.2                                                                          --CH.sub.2 O--CO-t-Bu                                                                    --CH.sub.2 O--CO-t-Bu                                                                    H    C                                            1413                                                                               p-NH.sub.2                                                                          --CH.sub.2 O--CO-t-Bu                                                                    --CH.sub.2 O--CO-t-Bu                                                                    H    C                                            1414                                                                               o-NO.sub.2                                                                          --CH.sub.2 O--CO-t-Bu                                                                    --CH.sub.2 O--CO-t-Bu                                                                    H    C                                            1415                                                                               m-NO.sub.2                                                                          --CH.sub.2 O--CO-t-Bu                                                                    --CH.sub.2 O--CO-t-Bu                                                                    H    C                                            1416                                                                               p-NO.sub.2                                                                          --CH.sub.2 O--CO-t-Bu                                                                    --CH.sub.2 O--CO-t-Bu                                                                    H    C                                            1417                                                                               o-OC.sub.2 H.sub.5                                                                  --CH.sub.2 O--CO-t-Bu                                                                    --CH.sub.2 O--CO-t-Bu                                                                    H    C                                            1418                                                                               m-OC.sub.2 H.sub.5                                                                  --CH.sub.2 O--CO-t-Bu                                                                    --CH.sub.2 O--CO-t-Bu                                                                    H    C                                            1419                                                                               p-OC.sub.2 H.sub.5                                                                  --CH.sub.2 O--CO-t-Bu                                                                    --CH.sub.2 O--CO-t-Bu                                                                    H    C                                            1420                                                                               p-I  --CH.sub.2 O--CO-t-Bu                                                                    --CH.sub.2 O--CO-t-Bu                                                                    H    C                                            1421                                                                               o-O-n-Pr                                                                            --CH.sub.2 O--CO-t-Bu                                                                    --CH.sub.2 O--CO-t-Bu                                                                    H    C                                            1422                                                                               m-O-n-Pr                                                                            --CH.sub.2 O--CO-t-Bu                                                                    --CH.sub.2 O--CO-t-Bu                                                                    H    C                                            1423                                                                               p-O-n-Pr                                                                            --CH.sub.2 O--CO-t-Bu                                                                    --CH.sub.2 O--CO-t-Bu                                                                    H    C                                            1424                                                                               o-O-i-Pr                                                                            --CH.sub.2 O--CO-t-Bu                                                                    --CH.sub.2 O--CO-t-Bu                                                                    H    C                                            1425                                                                               m-O-i-Pr                                                                            --CH.sub.2 O--CO-t-Bu                                                                    --CH.sub.2 O--CO-t-Bu                                                                    H    C                                            1426                                                                               p-O-i-Pr                                                                            --CH.sub.2 O--CO-t-Bu                                                                    --CH.sub.2 O--CO-t-Bu                                                                    H    C                                            1427                                                                               o-O-n-Bu                                                                            --CH.sub.2 O--CO-t-Bu                                                                    --CH.sub.2 O--CO-t-Bu                                                                    H    C                                            1428                                                                               m-O-n-Bu                                                                            --CH.sub.2 O--CO-t-Bu                                                                    --CH.sub.2 O--CO-t-Bu                                                                    H    C                                            1429                                                                               p-O-n-Bu                                                                            --CH.sub.2 O--CO-t-Bu                                                                    --CH.sub.2 O--CO-t-Bu                                                                    H    C                                            1430                                                                               o-O-i-Bu                                                                            --CH.sub.2 O--CO-t-Bu                                                                    --CH.sub.2 O--CO-t-Bu                                                                    H    C                                            1431                                                                               m-O-i-Bu                                                                            --CH.sub.2 O--CO-t-Bu                                                                    --CH.sub.2 O--CO-t-Bu                                                                    H    C                                            1432                                                                               p-O-i-Bu                                                                            --CH.sub.2 O--CO-t-Bu                                                                    --CH.sub.2 O--CO-t-Bu                                                                    H    C                                            1433                                                                               o-OCF.sub.3                                                                         --CH.sub.2 O--CO-t-Bu                                                                    --CH.sub.2 O--CO-t-Bu                                                                    H    C                                            1434                                                                               m-OCF.sub.3                                                                         --CH.sub.2 O--CO-t-Bu                                                                    --CH.sub.2 O--CO-t-Bu                                                                    H    C                                            1435                                                                               p-OCF.sub.3                                                                         --CH.sub.2 O--CO-t-Bu                                                                    --CH.sub.2 O--CO-t-Bu                                                                    H    C                                            1436                                                                               H    --CH.sub.2 O--CO-t-Bu                                                                    --CH.sub.2 O--CO-t-Bu                                                                    Me-- C                                            1437                                                                               o-OCH.sub.3                                                                         --CH.sub.2 O--CO-t-Bu                                                                    --CH.sub.2 O--CO-t-Bu                                                                    Me-- C                                            1438                                                                               m-OCH.sub.3                                                                         --CH.sub.2 O--CO-t-Bu                                                                    --CH.sub.2 O--CO-t-Bu                                                                    Me-- C                                            1439                                                                               p-OCH.sub.3                                                                         --CH.sub.2 O--CO-t-Bu                                                                    --CH.sub.2 O--CO-t-Bu                                                                    Me-- C                                            1440                                                                               o-Cl --CH.sub.2 O--CO-t-Bu                                                                    --CH.sub.2 O--CO-t-Bu                                                                    Me-- C                                            1441                                                                               m-Cl --CH.sub.2 O--CO-t-Bu                                                                    --CH.sub.2 O--CO-t-Bu                                                                    Me-- C                                            1442                                                                               p-Cl --CH.sub.2 O--CO-t-Bu                                                                    --CH.sub.2 O--CO-t-Bu                                                                    Me-- C                                            1443                                                                               o-Br --CH.sub.2 O--CO-t-Bu                                                                    --CH.sub.2 O--CO-t-Bu                                                                    Me-- C                                            1444                                                                               m-Br --CH.sub.2 O--CO-t-Bu                                                                    --CH.sub.2 O--CO-t-Bu                                                                    Me-- C                                            1445                                                                               p-Br --CH.sub.2 O--CO-t-Bu                                                                    --CH.sub.2 O--CO-t-Bu                                                                    Me-- C                                            1446                                                                               o-NH.sub.2                                                                          --CH.sub.2 O--CO-t-Bu                                                                    --CH.sub.2 O--CO-t-Bu                                                                    Me-- C                                            1447                                                                               m-NH.sub.2                                                                          --CH.sub.2 O--CO-t-Bu                                                                    --CH.sub.2 O--CO-t-Bu                                                                    Me-- C                                            1448                                                                               p-NH.sub.2                                                                          --CH.sub.2 O--CO-t-Bu                                                                    --CH.sub.2 O--CO-t-Bu                                                                    Me-- C                                            1449                                                                               o-NO.sub.2                                                                          --CH.sub.2 O--CO-t-Bu                                                                    --CH.sub.2 O--CO-t-Bu                                                                    Me-- C                                            1450                                                                               m-NO.sub.2                                                                          --CH.sub.2 O--CO-t-Bu                                                                    --CH.sub.2 O--CO-t-Bu                                                                    Me-- C                                            1451                                                                               p-NO.sub.2                                                                          --CH.sub.2 O--CO-t-Bu                                                                    --CH.sub.2 O--CO-t-Bu                                                                    Me-- C                                            1452                                                                               o-OC.sub.2 H.sub.5                                                                  --CH.sub.2 O--CO-t-Bu                                                                    --CH.sub.2 O--CO-t-Bu                                                                    Me-- C                                            1453                                                                               m-OC.sub.2 H.sub.5                                                                  --CH.sub.2 O--CO-t-Bu                                                                    --CH.sub.2 O--CO-t-Bu                                                                    Me-- C                                            1454                                                                               p-OC.sub.2 H.sub.5                                                                  --CH.sub.2 O--CO-t-Bu                                                                    --CH.sub.2 O--CO-t-Bu                                                                    Me-- C                                            1455                                                                               p-I  --CH.sub.2 O--CO-t-Bu                                                                    --CH.sub.2 O--CO-t-Bu                                                                    Me-- C                                            1456                                                                               o-O-n-Pr                                                                            --CH.sub.2 O--CO-t-Bu                                                                    --CH.sub.2 O--CO-t-Bu                                                                    Me-- C                                            1457                                                                               m-O-n-Pr                                                                            --CH.sub.2 O--CO-t-Bu                                                                    --CH.sub.2 O--CO-t-Bu                                                                    Me-- C                                            1458                                                                               p-O-n-Pr                                                                            --CH.sub.2 O--CO-t-Bu                                                                    --CH.sub.2 O--CO-t-Bu                                                                    Me-- C                                            1459                                                                               o-O-i-Pr                                                                            --CH.sub.2 O--CO-t-Bu                                                                    --CH.sub.2 O--CO-t-Bu                                                                    Me-- C                                            1460                                                                               m-O-i-Pr                                                                            --CH.sub.2 O--CO-t-Bu                                                                    --CH.sub.2 O--CO-t-Bu                                                                    Me-- C                                            1461                                                                               p-O-i-Pr                                                                            --CH.sub.2 O--CO-t-Bu                                                                    --CH.sub.2 O--CO-t-Bu                                                                    Me-- C                                            1462                                                                               o-O-n-Bu                                                                            --CH.sub.2 O--CO-t-Bu                                                                    --CH.sub.2 O--CO-t-Bu                                                                    Me-- C                                            1463                                                                               m-O-n-Bu                                                                            --CH.sub.2 O--CO-t-Bu                                                                    --CH.sub.2 O--CO-t-Bu                                                                    Me-- C                                            1464                                                                               p-O-n-Bu                                                                            --CH.sub.2 O--CO-t-Bu                                                                    --CH.sub.2 O--CO-t-Bu                                                                    Me-- C                                            1465                                                                               o-O-i-Bu                                                                            --CH.sub.2 O--CO-t-Bu                                                                    --CH.sub.2 O--CO-t-Bu                                                                    Me-- C                                            1466                                                                               m-O-i-Bu                                                                            --CH.sub.2 O--CO-t-Bu                                                                    --CH.sub.2 O--CO-t-Bu                                                                    Me-- C                                            1467                                                                               p-O-i-Bu                                                                            --CH.sub.2 O--CO-t-Bu                                                                    --CH.sub.2 O--CO-t-Bu                                                                    Me-- C                                            1468                                                                               o-OCF.sub.3                                                                         --CH.sub.2 O--CO-t-Bu                                                                    --CH.sub.2 O--CO-t-Bu                                                                    Me-- C                                            1469                                                                               m-OCF.sub.3                                                                         --CH.sub.2 O--CO-t-Bu                                                                    --CH.sub.2 O--CO-t-Bu                                                                    Me-- C                                            1470                                                                               p-OCF.sub.3                                                                         --CH.sub.2 O--CO-t-Bu                                                                    --CH.sub.2 O--CO-t-Bu                                                                    Me-- C                                            1471                                                                               H    --CH.sub.2 O--CO-t-Bu                                                                    --CH.sub.2 O--CO-t-Bu                                                                    --CH.sub.2 F                                                                        C                                            1472                                                                               o-OCH.sub.3                                                                         --CH.sub.2 O--CO-t-Bu                                                                    --CH.sub.2 O--CO-t-Bu                                                                    --CH.sub.2 F                                                                        C                                            1473                                                                               m-OCH.sub.3                                                                         --CH.sub.2 O--CO-t-Bu                                                                    --CH.sub.2 O--CO-t-Bu                                                                    --CH.sub.2 F                                                                        C                                            1474                                                                               p-OCH.sub.3                                                                         --CH.sub.2 O--CO-t-Bu                                                                    --CH.sub.2 O--CO-t-Bu                                                                    --CH.sub.2 F                                                                        C                                            1475                                                                               o-Cl --CH.sub.2 O--CO-t-Bu                                                                    --CH.sub.2 O--CO-t-Bu                                                                    --CH.sub.2 F                                                                        C                                            1476                                                                               m-Cl --CH.sub.2 O--CO-t-Bu                                                                    --CH.sub.2 O--CO-t-Bu                                                                    --CH.sub.2 F                                                                        C                                            1477                                                                               p-Cl --CH.sub.2 O--CO-t-Bu                                                                    --CH.sub.2 O--CO-t-Bu                                                                    --CH.sub.2 F                                                                        C                                            1478                                                                               o-Br --CH.sub.2 O--CO-t-Bu                                                                    --CH.sub.2 O--CO-t-Bu                                                                    --CH.sub.2 F                                                                        C                                            1479                                                                               m-Br --CH.sub.2 O--CO-t-Bu                                                                    --CH.sub.2 O--CO-t-Bu                                                                    --CH.sub.2 F                                                                        C                                            1480                                                                               p-Br --CH.sub.2 O--CO-t-Bu                                                                    --CH.sub.2 O--CO-t-Bu                                                                    --CH.sub.2 F                                                                        C                                            1481                                                                               o-NH.sub.2                                                                          --CH.sub.2 O--CO-t-Bu                                                                    --CH.sub.2 O--CO-t-Bu                                                                    --CH.sub.2 F                                                                        C                                            1482                                                                               m-NH.sub.2                                                                          --CH.sub.2 O--CO-t-Bu                                                                    --CH.sub.2 O--CO-t-Bu                                                                    --CH.sub.2 F                                                                        C                                            1483                                                                               p-NH.sub.2                                                                          --CH.sub.2 O--CO-t-Bu                                                                    --CH.sub.2 O--CO-t-Bu                                                                    --CH.sub.2 F                                                                        C                                            1484                                                                               o-NO.sub.2                                                                          --CH.sub.2 O--CO-t-Bu                                                                    --CH.sub.2 O--CO-t-Bu                                                                    --CH.sub.2 F                                                                        C                                            1485                                                                               m-NO.sub.2                                                                          --CH.sub.2 O--CO-t-Bu                                                                    --CH.sub.2 O--CO-t-Bu                                                                    --CH.sub.2 F                                                                        C                                            1486                                                                               p-NO.sub.2                                                                          --CH.sub.2 O--CO-t-Bu                                                                    --CH.sub.2 O--CO-t-Bu                                                                    --CH.sub.2 F                                                                        C                                            1487                                                                               o-OC.sub.2 H.sub.5                                                                  --CH.sub.2 O--CO-t-Bu                                                                    --CH.sub.2 O--CO-t-Bu                                                                    --CH.sub.2 F                                                                        C                                            1488                                                                               m-OC.sub.2 H.sub.5                                                                  --CH.sub.2 O--CO-t-Bu                                                                    --CH.sub.2 O--CO-t-Bu                                                                    --CH.sub.2 F                                                                        C                                            1489                                                                               p-OC.sub.2 H.sub.5                                                                  --CH.sub.2 O--CO-t-Bu                                                                    --CH.sub.2 O--CO-t-Bu                                                                    --CH.sub.2 F                                                                        C                                            1490                                                                               p-I  --CH.sub.2 O--CO-t-Bu                                                                    --CH.sub.2 O--CO-t-Bu                                                                    --CH.sub.2 F                                                                        C                                            1491                                                                               o-O-n-Pr                                                                            --CH.sub.2 O--CO-t-Bu                                                                    --CH.sub.2 O--CO-t-Bu                                                                    --CH.sub.2 F                                                                        C                                            1492                                                                               m-O-n-Pr                                                                            --CH.sub.2 O--CO-t-Bu                                                                    --CH.sub.2 O--CO-t-Bu                                                                    --CH.sub.2 F                                                                        C                                            1493                                                                               p-O-n-Pr                                                                            --CH.sub.2 O--CO-t-Bu                                                                    --CH.sub.2 O--CO-t-Bu                                                                    --CH.sub.2 F                                                                        C                                            1494                                                                               o-O-i-Pr                                                                            --CH.sub.2 O--CO-t-Bu                                                                    --CH.sub.2 O--CO-t-Bu                                                                    --CH.sub.2 F                                                                        C                                            1495                                                                               m-O-i-Pr                                                                            --CH.sub.2 O--CO-t-Bu                                                                    --CH.sub.2 O--CO-t-Bu                                                                    --CH.sub.2 F                                                                        C                                            1496                                                                               p-O-i-Pr                                                                            --CH.sub.2 O--CO-t-Bu                                                                    --CH.sub.2 O--CO-t-Bu                                                                    --CH.sub.2 F                                                                        C                                            1497                                                                               o-O-n-Bu                                                                            --CH.sub.2 O--CO-t-Bu                                                                    --CH.sub.2 O--CO-t-Bu                                                                    --CH.sub.2 F                                                                        C                                            1498                                                                               m-O-n-Bu                                                                            --CH.sub.2 O--CO-t-Bu                                                                    --CH.sub.2 O--CO-t-Bu                                                                    --CH.sub.2 F                                                                        C                                            1499                                                                               p-O-n-Bu                                                                            --CH.sub.2 O--CO-t-Bu                                                                    --CH.sub.2 O--CO-t-Bu                                                                    --CH.sub.2 F                                                                        C                                            1500                                                                               o-O-i-Bu                                                                            --CH.sub.2 O--CO-t-Bu                                                                    --CH.sub.2 O--CO-t-Bu                                                                    --CH.sub.2 F                                                                        C                                            1501                                                                               m-O-i-Bu                                                                            --CH.sub.2 O--CO-t-Bu                                                                    --CH.sub.2 O--CO-t-Bu                                                                    --CH.sub.2 F                                                                        C                                            1502                                                                               p-O-i-Bu                                                                            --CH.sub.2 O--CO-t-Bu                                                                    --CH.sub.2 O--CO-t-Bu                                                                    --CH.sub.2 F                                                                        C                                            1503                                                                               o-OCF.sub.3                                                                         --CH.sub.2 O--CO-t-Bu                                                                    --CH.sub.2 O--CO-t-Bu                                                                    --CH.sub.2 F                                                                        C                                            1504                                                                               m-OCF.sub.3                                                                         --CH.sub.2 O--CO-t-Bu                                                                    --CH.sub.2 O--CO-t-Bu                                                                    --CH.sub.2 F                                                                        C                                            1505                                                                               p-OCF.sub.3                                                                         --CH.sub.2 O--CO-t-Bu                                                                    --CH.sub.2 O--CO-t-Bu                                                                    --CH.sub.2 F                                                                        C                                            1506                                                                               H    --CH.sub.2 O--CO-t-Bu                                                                    --CH.sub.2 O--CO-t-Bu                                                                    --CH.sub.2 OH                                                                       C                                            1507                                                                               o-OCH.sub.3                                                                         --CH.sub.2 O--CO-t-Bu                                                                    --CH.sub.2 O--CO-t-Bu                                                                    --CH.sub.2 OH                                                                       C                                            1508                                                                               m-OCH.sub.3                                                                         --CH.sub.2 O--CO-t-Bu                                                                    --CH.sub.2 O--CO-t-Bu                                                                    --CH.sub.2 OH                                                                       C                                            1509                                                                               p-OCH.sub.3                                                                         --CH.sub.2 O--CO-t-Bu                                                                    --CH.sub.2 O--CO-t-Bu                                                                    --CH.sub.2 OH                                                                       C                                            1510                                                                               o-Cl --CH.sub.2 O--CO-t-Bu                                                                    --CH.sub.2 O--CO-t-Bu                                                                    --CH.sub.2 OH                                                                       C                                            1511                                                                               m-Cl --CH.sub.2 O--CO-t-Bu                                                                    --CH.sub.2 O--CO-t-Bu                                                                    --CH.sub.2 OH                                                                       C                                            1512                                                                               p-Cl --CH.sub.2 O--CO-t-Bu                                                                    --CH.sub.2 O--CO-t-Bu                                                                    --CH.sub.2 OH                                                                       C                                            1513                                                                               o-Br --CH.sub.2 O--CO-t-Bu                                                                    --CH.sub.2 O--CO-t-Bu                                                                    --CH.sub.2 OH                                                                       C                                            1514                                                                               m-Br --CH.sub.2 O--CO-t-Bu                                                                    --CH.sub.2 O--CO-t-Bu                                                                    --CH.sub.2 OH                                                                       C                                            1515                                                                               p-Br --CH.sub.2 O--CO-t-Bu                                                                    --CH.sub.2 O--CO-t-Bu                                                                    --CH.sub.2 OH                                                                       C                                            1516                                                                               o-NH.sub.2                                                                          --CH.sub.2 O--CO-t-Bu                                                                    --CH.sub.2 O--CO-t-Bu                                                                    --CH.sub.2 OH                                                                       C                                            1517                                                                               m-NH.sub.2                                                                          --CH.sub.2 O--CO-t-Bu                                                                    --CH.sub.2 O--CO-t-Bu                                                                    --CH.sub.2 OH                                                                       C                                            1518                                                                               p-NH.sub.2                                                                          --CH.sub.2 O--CO-t-Bu                                                                    --CH.sub.2 O--CO-t-Bu                                                                    --CH.sub.2 OH                                                                       C                                            1519                                                                               o-NO.sub.2                                                                          --CH.sub.2 O--CO-t-Bu                                                                    --CH.sub.2 O--CO-t-Bu                                                                    --CH.sub.2 OH                                                                       C                                            1520                                                                               m-NO.sub.2                                                                          --CH.sub.2 O--CO-t-Bu                                                                    --CH.sub.2 O--CO-t-Bu                                                                    --CH.sub.2 OH                                                                       C                                            1521                                                                               p-NO.sub.2                                                                          --CH.sub.2 O--CO-t-Bu                                                                    --CH.sub.2 O--CO-t-Bu                                                                    --CH.sub.2 OH                                                                       C                                            1522                                                                               o-OC.sub.2 H.sub.5                                                                  --CH.sub.2 O--CO-t-Bu                                                                    --CH.sub.2 O--CO-t-Bu                                                                    --CH.sub.2 OH                                                                       C                                            1523                                                                               m-OC.sub.2 H.sub.5                                                                  --CH.sub.2 O--CO-t-Bu                                                                    --CH.sub.2 O--CO-t-Bu                                                                    --CH.sub.2 OH                                                                       C                                            1524                                                                               p-OC.sub.2 H.sub.5                                                                  --CH.sub.2 O--CO-t-Bu                                                                    --CH.sub.2 O--CO-t-Bu                                                                    --CH.sub.2 OH                                                                       C                                            1525                                                                               p-I  --CH.sub.2 O--CO-t-Bu                                                                    --CH.sub.2 O--CO-t-Bu                                                                    --CH.sub.2 OH                                                                       C                                            1526                                                                               o-O-n-Pr                                                                            --CH.sub.2 O--CO-t-Bu                                                                    --CH.sub.2 O--CO-t-Bu                                                                    --CH.sub.2 OH                                                                       C                                            1527                                                                               m-O-n-Pr                                                                            --CH.sub.2 O--CO-t-Bu                                                                    --CH.sub.2 O--CO-t-Bu                                                                    --CH.sub.2 OH                                                                       C                                            1528                                                                               p-O-n-Pr                                                                            --CH.sub.2 O--CO-t-Bu                                                                    --CH.sub.2 O--CO-t-Bu                                                                    --CH.sub.2 OH                                                                       C                                            1529                                                                               o-O-i-Pr                                                                            --CH.sub.2 O--CO-t-Bu                                                                    --CH.sub.2 O--CO-t-Bu                                                                    --CH.sub.2 OH                                                                       C                                            1530                                                                               m-O-i-Pr                                                                            --CH.sub.2 O--CO-t-Bu                                                                    --CH.sub.2 O--CO-t-Bu                                                                    --CH.sub.2 OH                                                                       C                                            1531                                                                               p-O-i-Pr                                                                            --CH.sub.2 O--CO-t-Bu                                                                    --CH.sub.2 O--CO-t-Bu                                                                    --CH.sub.2 OH                                                                       C                                            1532                                                                               o-O-n-Bu                                                                            --CH.sub.2 O--CO-t-Bu                                                                    --CH.sub.2 O--CO-t-Bu                                                                    --CH.sub.2 OH                                                                       C                                            1533                                                                               m-O-n-Bu                                                                            --CH.sub.2 O--CO-t-Bu                                                                    --CH.sub.2 O--CO-t-Bu                                                                    --CH.sub.2 OH                                                                       C                                            1534                                                                               p-O-n-Bu                                                                            --CH.sub.2 O--CO-t-Bu                                                                    --CH.sub.2 O--CO-t-Bu                                                                    --CH.sub.2 OH                                                                       C                                            1535                                                                               o-O-i-Bu                                                                            --CH.sub.2 O--CO-t-Bu                                                                    --CH.sub.2 O--CO-t-Bu                                                                    --CH.sub.2 OH                                                                       C                                            1536                                                                               m-O-i-Bu                                                                            --CH.sub.2 O--CO-t-Bu                                                                    --CH.sub.2 O--CO-t-Bu                                                                    --CH.sub.2 OH                                                                       C                                            1537                                                                               p-O-i-Bu                                                                            --CH.sub.2 O--CO-t-Bu                                                                    --CH.sub.2 O--CO-t-Bu                                                                    --CH.sub.2 OH                                                                       C                                            1538                                                                               o-OCF.sub.3                                                                         --CH.sub.2 O--CO-t-Bu                                                                    --CH.sub.2 O--CO-t-Bu                                                                    --CH.sub.2 OH                                                                       C                                            1539                                                                               m-OCF.sub.3                                                                         --CH.sub.2 O--CO-t-Bu                                                                    --CH.sub.2 O--CO-t-Bu                                                                    --CH.sub.2 OH                                                                       C                                            1540                                                                               p-OCF.sub.3                                                                         --CH.sub.2 O--CO-t-Bu                                                                    --CH.sub.2 O--CO-t-Bu                                                                    --CH.sub.2 OH                                                                       C                                            1541                                                                               H    --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           H    C                                            1542                                                                               o-OCH.sub.3                                                                         --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           H    C                                            1543                                                                               m-OCH.sub.3                                                                         --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           H    C                                            1544                                                                               p-OCH.sub.3                                                                         --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           H    C                                            1545                                                                               o-Cl --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           H    C                                            1546                                                                               m-Cl --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           H    C                                            1547                                                                               p-Cl --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           H    C                                            1548                                                                               o-Br --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           H    C                                            1549                                                                               m-Br --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           H    C                                            1550                                                                               p-Br --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           H    C                                            1551                                                                               o-NH.sub.2                                                                          --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           H    C                                            1552                                                                               m-NH.sub.2                                                                          --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           H    C                                            1553                                                                               p-NH.sub.2                                                                          --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           H    C                                            1554                                                                               o-NO.sub.2                                                                          --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           H    C                                            1555                                                                               m-NO.sub.2                                                                          --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           H    C                                            1556                                                                               p-NO.sub.2                                                                          --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           H    C                                            1557                                                                               o-OC.sub.2 H.sub.5                                                                  --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           H    C                                            1558                                                                               m-OC.sub.2 H.sub.5                                                                  --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           H    C                                            1559                                                                               p-OC.sub.2 H.sub.5                                                                  --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           H    C                                            1560                                                                               p-I  --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           H    C                                            1561                                                                               o-O-n-Pr                                                                            --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           H    C                                            1562                                                                               m-O-n-Pr                                                                            --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           H    C                                            1563                                                                               p-O-n-Pr                                                                            --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           H    C                                            1564                                                                               o-O-i-Pr                                                                            --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           H    C                                            1565                                                                               m-O-i-Pr                                                                            --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           H    C                                            1566                                                                               p-O-i-Pr                                                                            --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           H    C                                            1567                                                                               o-O-n-Bu                                                                            --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           H    C                                            1568                                                                               m-O-n-Bu                                                                            --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           H    C                                            1569                                                                               p-O-n-Bu                                                                            --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           H    C                                            1570                                                                               o-O-i-Bu                                                                            --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           H    C                                            1571                                                                               m-O-i-Bu                                                                            --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           H    C                                            1572                                                                               p-O-i-Bu                                                                            --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           H    C                                            1573                                                                               o-OCF.sub.3                                                                         --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           H    C                                            1574                                                                               m-OCF.sub.3                                                                         --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           H    C                                            1575                                                                               p-OCF.sub.3                                                                         --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           H    C                                            1576                                                                               H    --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           Me-- C                                            1577                                                                               o-OCH.sub.3                                                                         --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           Me-- C                                            1578                                                                               m-OCH.sub.3                                                                         --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           Me-- C                                            1579                                                                               p-OCH.sub.3                                                                         --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           Me-- C                                            1580                                                                               o-Cl --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           Me-- C                                            1581                                                                               m-Cl --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           Me-- C                                            1582                                                                               p-Cl --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           Me-- C                                            1583                                                                               o-Br --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           Me-- C                                            1584                                                                               m-Br --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           Me-- C                                            1585                                                                               p-Br --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           Me-- C                                            1586                                                                               o-NH.sub.2                                                                          --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           Me-- C                                            1587                                                                               m-NH.sub.2                                                                          --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           Me-- C                                            1588                                                                               p-NH.sub.2                                                                          --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           Me-- C                                            1589                                                                               o-NO.sub.2                                                                          --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           Me-- C                                            1590                                                                               m-NO.sub.2                                                                          --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           Me-- C                                            1591                                                                               p-NO.sub.2                                                                          --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           Me-- C                                            1592                                                                               o-OC.sub.2 H.sub.5                                                                  --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           Me-- C                                            1593                                                                               m-OC.sub.2 H.sub.5                                                                  --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           Me-- C                                            1594                                                                               p-OC.sub.2 H.sub.5                                                                  --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           Me-- C                                            1595                                                                               p-I  --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           Me-- C                                            1596                                                                               o-O-n-Pr                                                                            --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           Me-- C                                            1597                                                                               m-O-n-Pr                                                                            --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           Me-- C                                            1598                                                                               p-O-n-Pr                                                                            --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           Me-- C                                            1599                                                                               o-O-i-Pr                                                                            --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           Me-- C                                            1600                                                                               m-O-i-Pr                                                                            --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           Me-- C                                            1601                                                                               p-O-i-Pr                                                                            --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           Me-- C                                            1602                                                                               o-O-n-Bu                                                                            --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           Me-- C                                            1603                                                                               m-O-n-Bu                                                                            --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           Me-- C                                            1604                                                                               p-O-n-Bu                                                                            --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           Me-- C                                            1605                                                                               o-O-i-Bu                                                                            --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           Me-- C                                            1606                                                                               m-O-i-Bu                                                                            --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           CH2CH.sub.2 S--CO-i-Pr                                                                   Me-- C                                            1607                                                                               p-O-i-Bu                                                                            --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           Me-- C                                            1608                                                                               o-OCF.sub.3                                                                         --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           Me-- C                                            1609                                                                               m-OCF.sub.3                                                                         --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           Me-- C                                            1610                                                                               p-OCF.sub.3                                                                         --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           Me-- C                                            1611                                                                               H    --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           --CH.sub.2 F                                                                        C                                            1612                                                                               o-OCH.sub.3                                                                         --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           --CH.sub.2 F                                                                        C                                            1613                                                                               m-OCH.sub.3                                                                         --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           --CH.sub.2 F                                                                        C                                            1614                                                                               p-OCH.sub.3                                                                         --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           --CH.sub.2 F                                                                        C                                            1615                                                                               o-Cl --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           --CH.sub.2 F                                                                        C                                            1616                                                                               m-Cl --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           --CH.sub.2 F                                                                        C                                            1617                                                                               p-Cl --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           --CH.sub.2 F                                                                        C                                            1618                                                                               o-Br --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           --CH.sub.2 F                                                                        C                                            1619                                                                               m-Br --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           --CH.sub.2 F                                                                        C                                            1620                                                                               p-Br --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           --CH.sub.2 F                                                                        C                                            1621                                                                               o-NH.sub.2                                                                          --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           --CH.sub.2 F                                                                        C                                            1622                                                                               m-NH.sub.2                                                                          --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           --CH.sub.2 F                                                                        C                                            1623                                                                               p-NH.sub.2                                                                          --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           --CH.sub.2 F                                                                        C                                            1624                                                                               o-NO.sub.2                                                                          --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           --CH.sub.2 F                                                                        C                                            1625                                                                               m-NO.sub.2                                                                          --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           --CH.sub.2 F                                                                        C                                            1626                                                                               p-NO.sub.2                                                                          --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           --CH.sub.2 F                                                                        C                                            1627                                                                               o-OC.sub.2 H.sub.5                                                                  --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           --CH.sub.2 F                                                                        C                                            1628                                                                               m-OC.sub.2 H.sub.5                                                                  --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           --CH.sub.2 F                                                                        C                                            1629                                                                               p-OC.sub.2 H.sub.5                                                                  --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           --CH.sub.2 F                                                                        C                                            1630                                                                               p-I  --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           --CH.sub.2 F                                                                        C                                            1631                                                                               o-O-n-Pr                                                                            --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           --CH.sub.2 F                                                                        C                                            1632                                                                               m-O-n-Pr                                                                            --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           --CH.sub.2 F                                                                        C                                            1633                                                                               p-O-n-Pr                                                                            --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           --CH.sub.2 F                                                                        C                                            1634                                                                               o-O-i-Pr                                                                            --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           --CH.sub.2 F                                                                        C                                            1635                                                                               m-O-i-Pr                                                                            --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           --CH.sub.2 F                                                                        C                                            1636                                                                               p-O-i-Pr                                                                            --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           --CH.sub.2 F                                                                        C                                            1637                                                                               o-O-n-Bu                                                                            --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           --CH.sub.2 F                                                                        C                                            1638                                                                               m-O-n-Bu                                                                            --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           --CH.sub.2 F                                                                        C                                            1639                                                                               p-O-n-Bu                                                                            --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           --CH.sub.2 F                                                                        C                                            1640                                                                               o-O-i-Bu                                                                            --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           --CH.sub.2 F                                                                        C                                            1641                                                                               m-O-i-Bu                                                                            --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           --CH.sub.2 F                                                                        C                                            1642                                                                               p-O-i-Bu                                                                            --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           --CH.sub.2 F                                                                        C                                            1643                                                                               o-OCF.sub.3                                                                         --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           --CH.sub.2 F                                                                        C                                            1644                                                                               m-OCF.sub.3                                                                         --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           --CH.sub.2 F                                                                        C                                            1645                                                                               p-OCF.sub.3                                                                         --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           --CH.sub.2 F                                                                        C                                            1646                                                                               H    --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           --CH.sub.2 OH                                                                       C                                            1647                                                                               o-OCH.sub.3                                                                         --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           --CH.sub.2 OH                                                                       C                                            1648                                                                               m-OCH.sub.3                                                                         --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           --CH.sub.2 OH                                                                       C                                            1649                                                                               p-OCH.sub.3                                                                         --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           --CH.sub.2 OH                                                                       C                                            1650                                                                               o-Cl --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           --CH.sub.2 OH                                                                       C                                            1651                                                                               m-Cl --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           --CH.sub.2 OH                                                                       C                                            1652                                                                               p-Cl --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           --CH.sub.2 OH                                                                       C                                            1653                                                                               o-Br --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           --CH.sub.2 OH                                                                       C                                            1654                                                                               m-Br --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           --CH.sub.2 OH                                                                       C                                            1655                                                                               p-Br --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           --CH.sub.2 OH                                                                       C                                            1656                                                                               o-NH.sub.2                                                                          --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           --CH.sub.2 OH                                                                       C                                            1657                                                                               m-NH.sub.2                                                                          --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           --CH.sub.2 OH                                                                       C                                            1658                                                                               p-NH.sub.2                                                                          --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           --CH.sub.2 OH                                                                       C                                            1659                                                                               o-NO.sub.2                                                                          --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           --CH.sub.2 OH                                                                       C                                            1660                                                                               m-NO.sub.2                                                                          --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           --CH.sub.2 OH                                                                       C                                            1661                                                                               p-NO.sub.2                                                                          --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           --CH.sub.2 OH                                                                       C                                            1662                                                                               o-OC.sub.2 H.sub.5                                                                  --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           --CH.sub.2 OH                                                                       C                                            1663                                                                               m-OC.sub.2 H.sub.5                                                                  --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           --CH.sub.2 OH                                                                       C                                            1664                                                                               p-OC.sub.2 H.sub.5                                                                  --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           --CH.sub.2 OH                                                                       C                                            1665                                                                               p-I  --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           --CH.sub.2 OH                                                                       C                                            1666                                                                               o-O-n-Pr                                                                            --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           --CH.sub.2 OH                                                                       C                                            1667                                                                               m-O-n-Pr                                                                            --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           --CH.sub.2 OH                                                                       C                                            1668                                                                               p-O-n-Pr                                                                            --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           --CH.sub.2 OH                                                                       C                                            1669                                                                               o-O-i-Pr                                                                            --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           --CH.sub.2 OH                                                                       C                                            1670                                                                               m-O-i-Pr                                                                            --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           --CH.sub.2 OH                                                                       C                                            1671                                                                               p-O-i-Pr                                                                            --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           --CH.sub.2 OH                                                                       C                                            1672                                                                               o-O-n-Bu                                                                            --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           --CH.sub.2 OH                                                                       C                                            1673                                                                               m-O-n-Bu                                                                            --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           --CH.sub.2 OH                                                                       C                                            1674                                                                               p-O-n-Bu                                                                            --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           --CH.sub.2 OH                                                                       C                                            1675                                                                               o-O-i-Bu                                                                            --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           --CH.sub.2 OH                                                                       C                                            1676                                                                               m-O-i-Bu                                                                            --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           --CH.sub.2 OH                                                                       C                                            1677                                                                               p-O-i-Bu                                                                            --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           --CH.sub.2 OH                                                                       C                                            1678                                                                               o-OCF.sub.3                                                                         --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           --CH.sub.2 OH                                                                       C                                            1679                                                                               m-OCF.sub.3                                                                         --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           --CH.sub.2 OH                                                                       C                                            1680                                                                               p-OCF.sub.3                                                                         --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           --CH.sub.2 CH.sub.2 S--CO-i-Pr                                                           --CH.sub.2 OH                                                                       C                                            __________________________________________________________________________

As for the methods for preparing the compounds of the present invention, the compounds of the general formula (I) wherein both of R² and R³ are either C₁ -C₂ 2 alkyl groups or ethyl groups substituted with one or more halogen atoms can be synthesized, for example, according to the reaction scheme (I) and (2) set out below. In the schemes, R¹, R⁴ and X are the same as those defined above, and R⁵ represents C₁ -C₂ 2 alkyl group or an ethyl group substituted with one or more halogen atoms. The symbol "W" represents a leaving group such as a halogen atom, p-toluenesulfonyloxy group, methanesulfonyloxy group, or trifluoromethanesulfonyloxy group. ##STR3##

The compound of the above general formula (II) and the compound of the above general formula (III) are first allowed to react with each other at a temperature of from 10 to 250° C., preferably from 130° to 200° C. for 0.1 to 100 hours, preferably 3 to 24 hours. The compound of the above general formula (IV) obtained by the above reaction may be separated and purified by ordinary separation and purification processes such as distillation, adsorption, and partition chromatography as required. The compound of above general formula (IV) can be subjected to the reaction set out below without purification, although it may be separated and purified as described above. The compound of the above general formula (IV) and the compound of the above general formula (V) are then allowed to react with each other to afford a compound of the above general formula (I') in the presence of a base such as sodium carbonate, potassium carbonate, cesium carbonate, sodium hydride, potassium hydride, triethylamine, or diazabicycloundecene in a suitable solvent such as acetonitrile, tetrahydrofuran, dimethyl sulfoxide, dimethylformamide, or methylpyrrolidone at a temperature of from 10 to 200° C., preferably from 50 to 150° C., for 0.1 to 100 hours, preferably 1 to 10 hours.

Sources of the compound of the above general formula (II) used as the starting material in the reaction scheme (1), the compounds of the above general formula (III), and the compounds of the above general formula (V) are not particularly limited. For example, compounds as commercially available chemical reagents may be used, or alternatively, compounds appropriately prepared by methods per se known in the art can be used. For example, the compound of the formula (V) can be synthesized by heating the compound of the formula (VI) and the compound of the formula (VIII) set out below at a temperature in a range of from 50° to 100° C. in a suitable solvent such as acetonitrile or dimethyl sulfoxide.

The compounds of the above formula (I') can also be prepared according to the scheme described below, wherein R¹, R⁴ , R⁵, X, and W are the same as those defined above. ##STR4##

The compound represented by the above general formula (IV) obtained according to the Reaction Scheme (1) and the compound represented by the above formula (VI) are allowed to react with each other to afford the compound of the above formula (VII) in the presence of a base such as sodium carbonate, potassium carbonate, cesium carbonate, sodium hydride, potassium hydride, triethylamine, or diazabicycloundecene in a suitable solvent such as acetonitrile, tetrahydrofuran, dimethyl sulfoxide, dimethylformamide, or methylpyrrolidone at a temperature of from 10° to 200° C., preferably from 50° to 150° C., for 0.1 to 100 hours, preferably 0.5 to 10 hours. The compound represented by the above formula (VII) and the mercapto compound represented by the above general formula (VIII) or a salt thereof, e.g., sodium salt, potassium salt, lithium salt, triethylamine salt or the like, are allowed to react with each other to afford a compound of the formula (I') in a suitable solvent such as acetonitrile, tetrahydrofuran, dimethyl sulfoxide, dimethylformamide, or methylpyrrolidone, if desired, in the presence of a suitable tertiary amine, at a temperature of from 10° to 200° C., preferably from 70° to 120° C., for 0.1 to 100 hours, preferably 0.5 to 12 hours. These compounds of the formula (I') correspond to compounds of the formula (I) wherein both of R² and R³ are either C₁ -C₂ 2 alkyl groups or ethyl groups substituted with one or more halogen atoms. Sources of the compounds of the above general formula (VI) used as the starting material in the reaction scheme (2) are not particularly limited. For example, compounds as commercially available chemical reagents may be used, or alternatively, compounds appropriately prepared by methods per se known in the art can be used.

The compounds of the formula (I) in which R⁵ of the formula (I') is converted to other substituents can be prepared by further modifying the phosphate ester part of the compounds of the formula (I'). For example, compounds of the formula (I) wherein both of R² and R³ are hydrogen atoms can be obtained by hydrolyzing a compound of the above general formula (I'). Compounds of the formula (I) wherein R³ is hydrogen atom, a C₁ -C₂ 2 alkyl group, an acylthioethyl group, or an ethyl group substituted with one or more halogen atoms and R² is a C₁ -C₂ 2 alkyl group or an ethyl group substituted with one or more halogen atoms can be prepared by reacting a compound of the formula (I') with a compound of the following formula (IX); R⁶ OH wherein R⁶ represents hydrogen atom, a C₁ -C₂ 2 alkyl group, an acylthioethyl group, or an ethyl group substituted with one or more halogen atoms, in the absence or presence of a suitable solvent, e.g., a chlorinated solvent such as dichloromethane, pyridine, acetonitrile, tetrahydrofuran, dimethyl sulfoxide, dimethylformamide, methylpyrrolidone or the like, if desired, in the presence of an acid or an alkali, at a temperature of from 10° to 100° C., preferably from 20° to 30° C., for 0.1 to 100 hours, preferably 5 to 12 hours. ##STR5##

In the above scheme, R¹, R⁴, R⁵, R⁶, and X are the same as those defined above.

The compounds represented by the above general formula (I) wherein R² and R³ independently represent hydrogen atom, a C₁ -C₂ 2 alkyl group, an acylthioethyl group, or an ethyl group substituted with one or more halogen atoms can also be obtained according to the method described below. In the following scheme, R¹, R⁴, and X are the same as those defined above, and R⁷ and R⁸ independently represent hydrogen atom, C₁ -C₂ 2 alkyl group, an acylthioethyl group, or an ethyl group substituted with one or more halogen atoms, with the proviso that R⁷ and R⁸ do not simultaneously represent hydrogen atoms. ##STR6##

The compound of the general formula (I") and trimethylsilyldie thylamine are first subjected to a reaction in a suitable solvent, e.g., a chlorinated solvent such as dichloromethane, dichloroethane, or chloroform at room temperature for approximately 1 hour. In the reaction, trimethylsilyldiethylamine is used in an amount of at least 2 moles based on 1 mole of the compound of the above general formula (I"). After the reaction mixture is concentrated to dryness, a resulting residue is dissolved in a chlorinated solvent such as dichloromethane, and then oxalyl chloride is added in an amount of at least 2 moles based on 1 mole of the compound of the formula (I"). The mixture is subjected to a reaction in the presence of catalytic amount of dimethylformamide for approximately 1 hour under ice cooling and then about one hour at room temperature.

The compound of the formula (X) obtained after the evaporation of the solvent is allowed to react, generally without purification, with the compound of the formula (XI) and/or the compound of the formula (XII) in a suitable solvent, e.g., a chlorinated solvent such as dichloromethane, pyridine, acetonitrile, tetrahydrofuran, dimethyl sulfoxide, dimethylformamide, methylpyrrolidone or the like, at a temperature of from 10° to 100° C., preferably from 20° to 30° C. for 0.1 to 100 hours, preferably 5 to 12 hours. The resulting compounds of the formula (XIII) correspond to the compounds of the formula (I) wherein R² and R³ independently represent hydrogen atom, a C₁ -C₂ 2 alkyl group, acylthioethyl group, or an ethyl group substituted with one or more halogen atoms, with the proviso that R² and R³ do not simultaneously represent hydrogen atoms. The compounds of the formula (I") used as the starting material in the above reaction can be obtained by hydrolyzing the compounds of the formula (I') as described previously, or alternatively, the compounds can be efficiently obtained by reacting compounds of the formula (I') wherein R⁵ is a C₁ -C₂ 2 alkyl group with triethyliodosilane, trimethylbromosilane or the like.

The compounds of the formula (I) wherein both of R² and R³ are acyloxymethyl groups or the compounds wherein one of R² and R³ is an acyloxymethyl group and the other is hydrogen atom can be prepared by reacting a compound of the above formula (I") with an acyloxymethyl halide represented by the following formula (XIV): R⁹ Y wherein R⁹ represents an acyloxymethyl group and Y represents a chlorine atom, a bromine atom, or an iodine atom, in the presence of a base such as sodium carbonate, potassium carbonate, cesium carbonate, sodium hydride, potassium hydride, triethylamine, pyridine, diazabicycloundecene, or N,N'-cyclohexyl-4-morpholine-carboxamidine in a suitable solvent such as acetonitrile, tetrahydrofuran, dimethyl sulfoxide, dimethylformamide, or methylpyrrolidone at a temperature of from 0° to 200° C., preferably 10° to 100° C., for 1 to 300 hours, preferably 10 to 200 hours. Where both of R² and R³ are acyloxymethyl groups, 2 moles of the compound the formula (XIV) based on the compound of the formula (I") may be subjected to the reaction, and where only one of them is an acyloxymethyl group, an equimolar amount may be subjected to the reaction.

Compounds of the formula (I) wherein one of R² and R³ is an acyloxymethyl group and the other is a C₁ -C₂ 2 alkyl group, acylthioethyl group, or an ethyl group substituted with one or more halogen atoms can be prepared by first synthesizing compounds wherein one of R² and R³ is a C₁ -C₂ 2 alkyl group, an acylthioethyl group, or an ethyl group substituted with one or more halogen atoms and the other is hydrogen atom, and then these compounds are subjected to reactions with the compounds of the formula (XIV) according to the method described above.

Salts of the compounds of the formula (I) can be prepared, for example, by the following processes: reacting the compound of the formula (I') with a corresponding acid with stirring at a temperature of from -10° to 100° C., preferably from 10° to 50° C., for 0.1 to 20 hours, preferably 0.3 to 1 hour in a suitable solvent such as ethyl acetate, isopropanol, acetonitrile, tetrahydrofuran, dimethyl sulfoxide, dimethylformamide, or methylpyrrolidone.

The aforementioned processes are described solely by way of examples for the preparations of the compounds of the present invention represented by the formula (I), and the processes for preparing the compounds of the present invention are not limited to these processes. More specific explanations will be given in Examples of the specification as for the processes for preparing the compounds of the present invention. Therefore, one of ordinarily skilled artisan can prepare compounds that fall within the scope of the above formula (I) according to the foregoing general explanations and specific descriptions in Examples, and applying appropriate alterations and modifications thereto, if necessary. The compounds of the above general formula (I) obtained according to the aforementioned processes and salts thereof can be separated and purified by applying ordinary separation and purification procedures for nucleotides, e.g., recrystallization, adsorption, ion exchange, partition chromatography or the like.

The compounds of the present invention are useful as active ingredients of medicaments, and more specifically, useful as an active ingredient of antiviral agents as demonstrated by the test examples set out below. In addition, their anti-tumor activities are expected as verified with regard to other ionic phosphonate nucleotide analogues. Although viruses applicable by the medicament of the present invention are not particularly limited, specific examples include RNA viruses such as human immunodeficiency virus, influenza virus, or hepatitis C virus, and DNA viruses such as herpes simplex virus I, herpes simplex virus II, Cytomegalovirus, vericello-herpes zoster virus, or hepatitis B virus, and a more preferred example includes hepatitis B virus.

When the compounds of the present invention are used as medicaments, the compounds, per se, may be administered. However, it is preferred that pharmaceutical compositions comprising the aforementioned compounds as active ingredients may be manufactured by using pharmaceutically acceptable additives and subjected to administration. Components of the pharmaceutical composition may be determined depending on solubility and chemical properties of the compound, an administration route, an administration protocol and the like. For example, formulations in a form of granules, subtilized granules, powder, tablets, hard syrup, soft capsules, troches, syrup, emulsion, soft gelatin capsules, gel, paste, suspension, liposome suspension or the like may be orally administered, or alternatively, injectable formulations may be administered intravenously, intramuscularly, or subcutaneously. A powder for injection may be used after preparing an injectable formulation just before use.

As the pharmaceutically acceptable additives, organic or inorganic solid or liquid carriers may be used which are suitable for oral, enteral, parenteral or topical administrations. Examples of the solid carriers used for the preparation of solid formulations include lactose, sucrose, starch, talc, cellulose, dextrin, china clay, calcium carbonate, agar, pectin, stearic acid, magnesium stearate, lecithin, sodium chloride and the like. Examples of the liquid carriers for the preparation of liquid formulations for oral administration include glycerin, peanut oil, polyvinylpyrrolidone, olive oil, ethanol, benzyl alcohol, propylene glycol, physiological saline, and water. In addition to the carriers mentioned above, the pharmaceutical composition may contain, for example, additives such as moistening agents, suspension aids, sweetening agents, flavoring agents, colorants, and preservatives. Liquid formulations may be filled in capsules made of absorbable material such as gelatin. Examples of solvents or suspending mediums for the preparation of formulations for parenteral administration, i.e., injections, include water, propylene glycol, polyethylene glycol, benzyl alcohol, ethyl oleate, and lecithin.

The compounds of the present invention, in particular, the ester derivatives represented by the above formula (I'), have excellent oral absorbabilities as demonstrated in the test examples set out below. Therefore, oral administration is a preferred administration route for the medicament of the present invention. Manufacture of the aforementioned formulations can be carried out according to ordinary methods. Clinical dose of the medicament of the present invention may generally be, for the use of an oral administration, 0.1 to 500 mg/kg, preferably 1 to 50 mg/kg per day for an adult as the weight of the compound of the present invention. However, the aforementioned dose may be appropriately increased or decreased depending on age, conditions or symptoms, or the presence or absence of a co-administered drug. The above daily dose may be administered once a day, or dividedly administered twice or several times a day with appropriate intervals. A continual administration may be carried out at intervals of several days. For an administration by an injection, dose may be 0.01 to 50 mg/kg, preferably 0.1 to 5 mg/kg per day for an adult as the weight of the compound of the present invention.

EXAMPLES

The present invention will be more specifically explained by referring to the following examples. However, the scope of the present invention is not limited to the examples set out below. Compound numbers in the examples correspond to those listed in Table 1.

Example 1 Preparation of 2-amino-9- 2- bis(2,2,2-trifluoroethyl)-phosphonylmethoxy!ethyl!-6-phenylthiopurine (Compound No. 1)

2-Chloroethyl chloromethyl ether (87 g, 670 mmol) and Tris(2,2,2-trifluoroethyl)phosphite (200 g, 610 mmol) were heated at 160° C. for 7 hours to obtain 2- bis(2,2,2-trifluoroethyl) phosphonylmethoxy!ethyl chloride quantitatively.

2- Bis(2,2,2-trifluoroethyl)phosphonylmethoxy!ethyl chloride (206 g) was dissolved in methyl ethyl ketone (2,000 ml) and the solution was heated under reflux with sodium iodide (270 g) for 8 hours. After completion of the reaction, the mixture was cooled to room temperature and concentrated to dryness. The residue was dissolved in chloroform/hexane and adsorbed on a silica gel column, and then eluted with chloroform/hexane to give 2- bis(2,2,2-trifluoroethyl)-phosphonylmethoxy!ethyl iodide quantitatively.

2-Amino-6-chloropurine (15.0 g, 88 mmol) was suspended in dimethylformamide (360 ml) and treated with 1,8-diazabicyclo 5.4.0!-undec-7-ene (13.9 ml, 93 mmol) at 80° C. for 1 hour. Then, 2- bis(2,2,2-trifluoroethyl)phosphonylmethoxy!ethyl iodide (23.8 ml) was added to the reaction mixture and subjected to a reaction at 100° C. for 5 hours. After completion of the reaction, the mixture was cooled to room temperature and concentrated to dryness. The residue was dissolved in chloroform and adsorbed on a silica gel column, and then eluted with 5%-methanol in chloroform to give 2-amino-9- 2- bis(2,2,2-trifluoroethyl)phosphonylmethoxy!ethyl-6-chloropurine (23.3 g, yield 56%).

Triethylamine (2.1 ml) and thiophenol (3.1 ml) were added to a solution of 2-amino-9- 2- bis(2,2,2-trifluoroethyl)phosphonyl-methoxy!ethyl!-6-chloropurine (7.1 g) in dimethylformamide (68 ml) and the mixture was stirred at 100° C. for 2 hours. The reaction mixture was cooled to room temperature and concentrated to dryness. The residue was dissolved in chloroform and adsorbed on a silica gel column, and then eluted with 5%-methanol in chloroform to give 2-amino-9- 2- bis(2,2,2-trifluoroethyl)phosphonylmethoxy!ethyl!-6-phenylthiopurine (5.0 g, yield 61%).

m.p.:105°-106° C. (ethanol)

¹ H-NMR(CDCl₃, δ): 3.86-4.03(m,4H), 4.20-4.50(m,6H), 4.77(s,2H), 7.42-7.58(m,3H), 7.58-7.68(m,2H), 7.72(s,1H)

Example 2 Preparation of 2-amino-9- 2- bis(2,2,2-trifluoroethyl)-phosphonylmethoxy!ethyl!-6-p-nitrophenylthiopurine (Compound No. 16)

The title compound was obtained in a similar manner to Example 1 except that p-nitrothiophenol was used instead of thiophenol used in Example 1.

m. p.:114°-116° C. (diisopropyl ether)

¹ H-NMR(CDCl₃, δ): 3.87-4.02(m,4H), 4.22-4.46(m,6H), 4.83(s,2H), 7.75-7.85(m,2H), 8.20-8.28(m,2H)

Example 3 Preparation of 2-amino-9- 2- bis(2,2,2-trifluoroethyl)-phosphonylmethoxy!ethyl!-6-p-methoxyphenylthiopurine (Compound No. 4)

The title compound was obtained in a similar manner to Example 1 except that p-methoxythiophenol was used instead of thiophenol used in Example 1.

m.p.:93°-95° C. (diisopropyl ether)

¹ H-NMR(CDCl₃, δ): 3.85(s,3H), 3.92-4.00(m,4H), 4.24-4.45(m,6H), 4.75(s,2H), 6.95(d,J=9.0 Hz,2H), 7.53(d,J=9.0 Hz,2H), 7.71(s,1H)

Example 4 Preparation of 2-amino-9- 2- bis(2,2,2-trifluoroethyl)-phosphonylmethoxy!ethyl!-6-m-methoxyphenylthiopurine (Compound No. 3)

The title compound was obtained in a similar manner to Example 1 except that m-methoxythiophenol was used instead of thiophenol used in Example 1.

UV: λ_(max) =291, 328 (0.01N--HCl/CH₃ OH)

λ_(max) =242, 315 (0.01N--NaOH/CH₃ OH)

¹ H-NMR(CDCl₃, δ): 3.82(s,3H), 3.88-8.97(m,4H), 4.24-4.45(m,6H), 4.81(s,2H), 6.92-7.00(m,1H), 7.18-7.40(m,4H), 7.72(s,1H)

Example 5 Preparation of 2-amino-9- 2- bis(2,2,2-trifluoroethyl)-phosphonylmethoxy!ethyl!-6-o-methoxyphenylthiopurine (Compound No. 2)

The title compound was obtained in a similar manner to Example 1 except that o-methoxythiophenol was used instead of thiophenol used in Example 1.

UV: λ_(max) =332 (0.01N--HC1/CH₃ OH)

λ_(max) =314 (0.01N--NaOH/CH₃ OH)

¹ H-NMR(CDCl₃, δ): 3.80(s,3H), 3.85-3.98(m,4H), 4.20-4.46(m,6H), 4.78(s,2H), 6.96-7.04(m,2H), 7.43(ddd,J=7.7, 7.7, and 1.5 Hz,1H), 7.59(dd,J=7.6 and 1.5 Hz,1H), 7.69(s,1H)

Example 6 Preparation of 2-amino-9- 2- bis(2,2,2-trifluoroethyl)-phosphonylmethoxy!ethyl!-6-p-aminophenylthiopurine (Compound No. 13)

The title compound was obtained in a similar manner to Example 1 except that p-aminothiophenol was used instead of thiophenol used in Example 1.

m.p.:130-132° C. (diisopropyl ether)

¹ H-NMR(CDCl₃, δ): 3.86-4.00(m,4H), 4.21-4.48(m,6H), 4.80(s,2H), 6.71(d,J=8.5 Hz,2H), 7.38(d,J=8.5 Hz,2H), 7.70(s,1H)

Example 7 Preparation of 2-amino-9- 2- bis(2,2,2-trifluoroethyl)-phosphonylmethoxy!ethyl!-6-p-chlorophenylthiopurine (Compound No. 7)

The title compound was obtained in a similar manner to Example 1 except that p-chlorothiophenol was used instead of thiophenol used in Example 1.

m. p.: 108-110° C. (diisopropyl ether/hexane)

¹ H-NMR(CDCl₃, δ): 3.87-4.00(m,4H), 4.22-4.47(m,6H), 4.77(s,2H), 7.39(d,J=8.5 Hz,2H), 7.56(d,J=8.5 Hz,2H), 7.76(s,1H)

Example 8 Preparation of 2-amino-9- 2- bis(2,2,2-trifluoroethyl)-phosphonylmethoxy!ethyl!-6-p-ethoxyphenylthiopurine (Compound No. 19)

p-Hydroxybenzenethiol (25 g) was dissolved in DMSO (155 ml) and the solution was stirred for 4 hours and poured into ice water (1 L). The precipitated crystals were dried under reduced pressure to give bis(p-hydroxyphenyl)disulfide quantitatively.

Potassium carbonate (2.2 g) and ethyl iodide (4.3 g) were added to a solution of bis(p-hydroxyphenyl)disulfide (2.0 g) in DMF (20 ml), and the mixture was stirred at 70° C. for 16 hours and poured into ice water (100 ml). The mixture was extracted with hexane (500 ml) and concentrated to give bis(p-ethoxyphenyl)disulfide (1.8 g, 82%).

Triphenylphosphine (1.9 g) and concentrated hydrochloric acid (3 drops) were added to a solution of bis(p-ethoxyphenyl)disulfide (1.8 g) in 1,4-dioxane (20 ml) and water (5 ml). After stirring at 40° C. for 10 hours, the mixture was poured into chloroform (250 ml). After washing twice with water, the organic layer was concentrated to give p-ethoxybenzenethiol quantitatively. The title compound was obtained in a similar manner to Example 1 except that p-ethoxybenzenethiol was used instead of thiophenol.

m.p.: 61-64° C. (chloroform)

¹ H-NMR(CDCl₃, δ): 1.45(t,J=7.0 Hz,3H), 3.84-3.98(m,4H), 4.08(q,J=7.0 Hz,2H), 4.18-4.48(m,6H), 4.76(s,2H), 6.94(d,J=8.4 Hz,2H), 7.52(d,J=8.4 Hz,2H), 7.71(s,1H)

Example 9 Preparation of 2-amino-9- 2- bis(2,2,2-trifluoroethyl)-phosphonylmethoxy!ethyl!-6-p-butoxyphenylthiopurine (Compound No. 29)

The title compound was obtained in a similar manner to Example 2 except that butyl iodide was used instead of ethyl iodide.

m.p.: 89-92° C. (chloroform)

¹ H-NMR(CDCl₃, δ): 0.99(t,J=7.5 Hz,3H), 1.51(tq,J=8.1 Hz and 7.5 Hz,2H), 1.79(tt,J=6.4 Hz and 8.1 Hz,2H), 3.84-3.98(m,4H), 4.00(t,J=6.4 Hz,2H), 4.20-4.48(m,6H), 4.76(s,2H), 6.94(d,J=8.8 Hz,2H), 7.52(d,J=8.8 Hz,2H), 7.71(s,1H)

Example 10 Preparation of 2-amino-9- 2- bis(2,2,2-trifluoroethyl)-phosphonylmethoxy!ethyl!-6-p-propoxyphenylthiopurine (Compound No. 23)

The title compound was obtained in a similar manner to Example 8 except that propyl iodide was used instead of ethyl iodide.

UV: λ_(max) =229, 331 (0.01N--HCl/CH₃ OH)

λ_(max) =223, 314 (0.01N--NaOH/CH₃ OH)

¹ H-NMR(CDCl₃, δ): 1.05(t,J=7.4 Hz,3H), 1.84(tq,J=6.8 Hz and 7.4 Hz,2H), 3.82-4.00(m,6H), 4.20-4.48(m,6H), 4.78(s,2H), 6.95(d,J=8.7 Hz,2H), 7.51(d,J=8.7 Hz,2H), 7.71(s,1H)

Example 11 Preparation of 2-amino-9- 2- bis(2,2,2-trifluoroethyl)-phosphonylmethoxy!ethyl!-6-p-isopropoxyphenylthiopurine (Compound No. 26)

The title compound was obtained in a similar manner to Example 8 except that p-isopropyl iodide was used instead of ethyl iodide.

UV: λ_(max) =230, 330 (0.01N--HCl/CH₃ OH)

λ_(max) =223, 314 (0.01N--NaOH/CH₃ OH)

¹ H-NMR(CDCl₃, δ): 1.37(d,J=6.0 Hz,6H), 3.85-3.98(m,4H), 4.18-4.48(m,6H), 4.60(septet,J=6.0 Hz,1H), 4.77(s,2H), 6.93(d,J=8.7 Hz,2H), 7.51(d,J=8.7 Hz,2H), 7.71(s,1H)

Example 12 Preparation of 2-amino-9- 2- bis(2,2,2-trifluoroethyl)-phosphonylmethoxy!ethyl!-6-p-isobutoxyphenylthiopurine (Compound No. 32)

The title compound was obtained in a similar manner to Example 8 except that p-isobutyl iodide was used instead of ethyl iodide.

UV: λ_(max) =230, 331 (0.01N--HCl/CH₃ OH)

λ_(max) =223, 314 (0.01N--NaOH/CH₃ OH)

¹ H-NMR(CDCl₃, δ): 1.05(d,J=6.8 Hz,6H), 2.13(apparent quintet,J=6.5 Hz,1H), 3.76(d,J=6.5 Hz,2H), 3.83-3.97(m,4H), 4.20-4.45(m,6H), 4.77(s,2H), 6.94(d,J=8.9 Hz,2H), 7.52(d,J=8.9 Hz,2H), 7.71(s,1H)

Example 13 Preparation of 2-amino-9- 2- bis(2,2,2-trifluoroethyl)-phosphonylmethoxy!ethyl!-6-p-trifluoromethoxyphenylthiopurine (Compound No. 35)

Zinc powder (3.1 g) was added to a suspension of p-trifluoromethoxybenzenesulfonyl chloride (1.36 ml) in concentrated sulfuric acid (3.4 ml) and water (20 ml), and the suspension was stirred at 0° C. for 18 hours and heated under reflux for 6 hours. The mixture was added with ethyl acetate, washed with water, saturated aqueous solution of sodium hydrogen carbonate, and saturated brine, and then concentrated under reduced pressure to give p-trifluoromethoxybenzenethiol (0.73 g, 47%).

The title compound was obtained in a similar manner to Example 1 except that p-trifluoromethoxybenzenethiol was used instead of thiophenol.

m.p.: 128-130° C. (chloroform)

¹ H-NMR(CDCl₃, δ): 3.86-3.98(m,4H), 4.22-4.48(m,6H), 4.78(s,2H), 7.27(d,J=8.7 Hz,2H), 7.66(d,J=8.7 Hz,2H), 7.73(s,1H)

Example 14 Preparation of 2-amino-9- 2- (2,2,2-trifluoroethyl)-phosphonylmethoxy!ethyl!-6-phenylthiopurine (Compound No. 211)

1N aqueous solution of sodium hydroxide (82 μl) was added to a solution of 2-amino-9- 2- bis(2,2,2-trifluoroethyl) phosphonylmethoxy!ethyl!-6-phenylthiopurine (45 mg) in tetrahydrofuran (0.3 ml), and the mixture was stirred for 30 minutes and then lyophilized to give 2-amino-9- 2- phosphonylmethoxy!ethyl!-6-phenylthiopurine (37 mg, 93%).

UV: λ_(max) =325 (0.1N--HCl/CH₃ OH)

λ_(max) =244, 316 (0.1N--NaOH/CH₃ OH)

¹ H-NMR(D₂ O, δ): 3.63(d,J=8.8 Hz,2H), 3.81-4.04(m,4H), 4.23-4.34(m,2H), 7.40-7.66(m,5H), 8.01(s,1H)

Example 15 Preparation of 2-amino-9- 2- (2,2,2-trifluoroethyl)-phosphonylmethoxy!ethyl!-6-p-methoxyphenylthiopurine (Compound No. 214)

The title compound was obtained in a similar manner to Example 14 except that 2-amino-9- 2- bis(2,2,2-trifluoroethyl) phosphonylmethoxy!ethyl!-6-p-methoxyphenylthiopurine was used instead of 2-amino-9- 2- bis(2,2,2-trifluoroethyl) phosphonylmethoxy!-ethyl!-6-phenylthiopurine.

UV: λ_(max) =230, 328 (0.1N--HCl/CH₃ OH)

λ_(max) =223, 314 (0.01N--NaOH/CH₃ OH) ¹ H-NMR(D₂ O, δ): 3.69(d,J=8.8 Hz,2H), 3.82-4.06(m involving s at 3.87,7H), 4.28-4.38(m,2H), 7.05(d,J=8.7 Hz,2H), 7.51(d,J=8.7 Hz,2H), 8.04(s,1H)

Example 16 Preparation of 2-amino-9- 2- phosphonylmethoxy!ethyl!-6-phenylthiopurine (Compound No. 281)

2-Amino-9- 2- diethylphosphonylmethoxy!ethyl!-6-phenylthiopurine was obtained in a similar manner to Example 1 except that triethylphosphite was used instead of tris(2,2,2-trifluoroethyl)phosphite.

Bromotrimethylsilane (2.6 ml) was added to a solution of 2-amino-9- 2- diethylphosphonylmethoxy!ethyl!-6-phenylthiopurine (1.75 g) in acetonitrile (20 ml) and the mixture was stirred at 25° C. for 22 hours. The mixture was added with water and concentrated to dryness, and the product was crystallized from acetone/methanol to give 2-amino-9- 2- phosphonylmethoxy!ethyl!-6-phenylthiopurine (406 mg, 27%).

m.p.: 163-168° C. (dec. acetone/methanol)

¹ H-NMR(DMSO-d₆, δ): 3.58(d,J=8.7 Hz,2H), 3.81(t,J=5.1 Hz,2H), 4.19(t,J=5.1 Hz,2H), 7.40-7.50(m,3H), 7.55-7.66(m,2H), 8.02(s,1H)

Example 17 Preparation of 2-amino-9- 2-phosphonylmethoxyethyl!-6-p-methoxyphenylthiopurine (Compound No. 284)

The title compound was obtained in a similar manner to Example 16 except that p-methoxythiophenol was used instead of thiophenol.

UV: λ_(max) =230, 328 (0.1N--HCl/CH₃ OH)

λ_(max) =223, 314 (0.01N--NaOH/CH₃ OH)

¹ H-NMR(DMSO-d₆, δ): 3.58(d,J=8.6 Hz,2H), 3.78-3.92 (m involving s at 3.79,5H), 4.18-4.30(m,2H), 7.02(d,J=8.7 Hz,2H), 7.51(d,J=8.7 Hz,2H), 8.14(s,1H)

Example 18 Preparation of 2-amino-9- 2- bis(2,2,2-trifluoroethyl)-phosphonylmethoxy!ethyl!-6-p-methoxyphenylthiopurine hydrochloride

A solution of 2-amino-9- 2- bis(2,2,2-trifluoroethyl) phosphonylmethoxy!ethyl!-6-p-methoxyphenylthiopurine in ethyl acetate was added dropwise to a solution of hydrogen chloride in ethyl acetate and the mixture was stirred for 30 minutes. The precipitated crystals were dried under reduced pressure to give 2-amino-9- 2- bis(2,2,2-trifluoroethyl)phosphonylmethoxy!ethyl!-6-p-methoxyphenylthiopurine hydrochloride.

m.p.: 110-115° C. (dec. ethyl acetate)

¹ H-NMR(DMSO-d₆, δ): 3.79(s,3H), 3.87(t,J=4.8 Hz,2H), 4.13(d,J=7.9 Hz,2H), 4.23(t,J=4.8 Hz,2H), 4.55-4.75(m,4H), 7.02(d,J=8.7 Hz,2H), 7.49(d,J=8.7 Hz,2H), 8.13(s,1H)

Example 19 Preparation of 2-amino-9- 2- bis(2,2,2-trifluoroethyl)-phosphonylmethoxy!ethyl!-6-m-methoxyphenylthiopurine hydrochloride

A solution of 2-amino-9- 2- bis(2,2,2-trifluoroethyl) phosphonylmethoxy!ethyl!-6-m-methoxyphenylthiopurine in ethyl acetate was added dropwise to a solution of hydrogen chloride in ethyl acetate and the mixture was stirred for 30 minutes. The precipitated crystals were dried under reduced pressure to give 2-amino-9- 2- bis(2,2,2-trifluoroethyl)phosphonylmethoxy!ethyl!-6-m-methoxyphenylthiopurine hydrochloride.

m.p.: 130-135° C. (dec. ethyl acetate)

¹ H-NMR(DMSO-d₆, δ): 3.77(s,3H), 3.84-3.96(m,2H), 4.14(d,J=8.0 Hz,2H), 4.20-4.36(m,2H), 4.56-4.76(m,4H), 6.99-7.08(m,1H), 7.12-7.24(m,2H), 7.36(dd,J=7.8 Hz and 8.3 Hz,1H), 8.28(s,1H)

Example 20 Preparation of 2-amino-9- 2- bis(2,2,2-trifluoroethyl)-phosphonylmethoxy!ethyl!-6-o-methoxyphenylthiopurine hydrochloride

A solution of 2-amino-9- 2- bis(2,2,2-trifluoroethyl) phosphonylmethoxy!ethyl!-6-o-methoxyphenylthiopurine in ethyl acetate was added dropwise to a solution of hydrogen chloride in ethyl acetate and the mixture was stirred for 30 minutes. The precipitated crystals were dried under reduced pressure to give 2-amino-9- 2- bis(2,2,2-trifluoroethyl)phosphonylmethoxy!ethyl!-6-o-methoxyphenylthiopurine hydrochloride.

m.p.: 101-106° C. (dec. ethyl acetate)

¹ H-NMR(DMSO-d₆, δ): 3.74(s,3H), 3.84-3.98(m,2H), 4.14(d,J=7.9 Hz,2H), 4.20-4.34(m,2H), 4.56-4.76(m,4H), 7.01(dd,J=7.5 Hz,1H), 7.14(d,J=8.4 Hz,1H), 7.42-7.60(m,2H), 8.27(s,1H)

Example 21 Preparation of 2-amino-9- 2- bis(2,2,2-trifluoroethyl)-phosphonylmethoxy!propyl!-6-phenylthiopurine (Compound No. 351)

1-Chloro-2-propanol (25 ml) and paraformaldehyde (11 g) were suspended in dichloromethane (50 ml), and the suspension was cooled to 0° C. and stirred for 10 hours with hydrogen chloride gas bubbling. After evaporation of dichloromethane, the residue was added with tris(2,2,2-trifluoroethyl)phosphite (86.5 g) and heated at 160° C. for 5 hours. The reaction mixture was evaporated under reduced pressure to give 2- bis(2,2,2-trifluoroethyl)-phosphonylmethoxy!propyl chloride.

2-Amino-6-chloropurine (15.0 g, 88 mmol) was suspended in dimethylformamide (360 ml) and reacted with 1,8-diazabicyclo 5.4.0!-undec-7-ene (13.9 ml, 93 mmol) at 80° C. for 1 hour. Then, 2- bis(2,2,2-trifluoroethyl)phosphonylmethoxy!propyl chloride (36.1 g) was added to the above reaction mixture and subjected to a reaction at 100° C. for 2 hours. After completion of the reaction, the mixture was cooled to room temperature and concentrated. The residue was added with water and extracted with ethyl acetate. After the organic layer was dried over magnesium sulfate, the layer was concentrated to give syrup. The resulting syrup was dissolved in ether and insoluble materials were removed to give 2-amino-9- 2- bis(2,2,2-trifluoroethyl)phosphonylmethoxy!propyl!-6-chloropurine (6 g).

Triethylamine (1.1 ml) and thiophenol (1.53 ml) were added to a solution of 2-amino-9- 2- bis(2,2,2-trifluoroethyl)-phosphonylmethoxy!propyl!-6-chloropurine (3.0 g) in dimethylformamide (25 ml) and the mixture was stirred at 100° C. for 2 hours. The reaction mixture was cooled to room temperature and concentrated. The residue was added with an aqueous sodium hydrogen carbonate and extracted with ethyl acetate, and the organic layer was concentrated. The residue was dissolved in chloroform and adsorbed on a silica gel column, and then eluted with 2%-methanol in chloroform to give 2-amino-9- 2- bis(2,2,2-trifluoroethyl)phosphonylmethoxy!propyl!-6-phenylthiopurine (0.77 g, yield 22%).

m.p.: 119-120° C. (isopropyl ether)

¹ H-NMR(CDCl₃, δ): 1.25(d,J=5.9 Hz,3H), 3.76-4.23(m,5H), 4.28-4.42(m,4H), 4.77(s,2H), 7.40-7.43 (m,3H), 7.62-7.65(m,2H), 7.72(s,1H)

Example 22 Preparation of 2-amino-9- 2- bis(2,2,2-trifluoroethyl)-phosphonylmethoxy!propyl!-6-p-methoxyphenylthiopurine (Compound No. 354)

The title compound was obtained in a similar manner to Example 21 except that p-methoxythiophenol was used instead of thiophenol.

m.p.: 118-119° C. (diisopropyl ether)

¹ H-NMR(CDCl₃, δ): 1.24(d,J=5.9 Hz,3H), 3.81-4.02(m,5H), 3.85(s,3H), 4.31-4.40(m,4H), 4.75(s,2H), 6.95(d,J=8.7 Hz,2H), 7.53(d,J=8.7 Hz,2H), 7.71(s,1H)

Test Example 1 Inhibitory activity against the growth of Hepatitis B virus (HBV)

HBV growth inhibitory activities of the compounds of the present invention were measured by a conventional method (K. Ueda, et al., Virology, 169, pp.213-216, 1989). HB611 cells (2×10⁴, recombinant human hepatocellular carcinoma cells producing HBV) were cultured in Dulbecco ME medium containing 10% fetal bovine serum, streptomycin (100 μg/ml), penicillin (100 IU/ml), and Geneteicin (trade name, the antibiotic manufactured by Life Technologies, Co., Ltd., 0.2 mg/ml) at 37° C. The medium was changed with fresh medium on the second day and fifth day of the culture, and then the medium was changed with a medium containing a test compound at a final concentration of 0.005-100 mM after 8, 11, and 14 days of the culture. Total cellular DNAs were collected on the 17th day of the culture. Amounts of the HBV-DNAs in the cells were measured by the Southern blotting method, and concentrations achieving 50% inhibition of cytoplasmic HBV-DNA synthesis were determined. concentrations of compounds required for 50% extinction of HB611 cells were also determined. Results are shown in Table 2.

In the table, the compound numbers correspond to those listed in Table 1. Table 2 also shows as reference the results obtained by similar tests using the known compounds, i.e., dipivaloyloxymethyl ester of PMEA (Reference Example 1) and 9- 2- bis(2,2,2-trifluoroethyl)phosphonylmethoxy!ethyl!-2-amino-6-p-toluylthiopurine disclosed in EP 632048 (Reference Example 2).

                  TABLE 2                                                          ______________________________________                                                   50% inhibitory  50% cytotoxic                                        Compound  concentration against                                                                          concentration against                                No.       HBV-DNA synthesis (μM)                                                                      HB611 cells (μM)                                  ______________________________________                                         No.1      0.01            >1,000                                               No.2      0.08            >1,000                                               No.3      0.04            >1,000                                               No.4      0.05            >1,000                                               Reference 1 .sup.a                                                                       18.8                11                                               Reference 2 .sup.b                                                                       0.06                108                                              ______________________________________                                          .sup.a dipivaloyloxymethyl ester of PMEA                                       .sup.b                                                                         9 2 bis(2,2,2trifluoroethyl)phosphonylmethoxy!ethyl2-amino-6-p-toluylthio     urine                                                                           ##STR7##                                                                        Test Example 2                                                            

HBV growth inhibitory activity of mouse serum after oral administration

Groups of mice each consisting of three mice were administered orally with a test compound at a single dose of 1 g/kg or 0.3 g/kg. Blood was collected 30 minutes after the administration, and serum was prepared. HB611 cells (2×10⁴, recombinant human hepatocellular carcinoma cells producing HBV) were cultured in Dulbecco ME medium containing 10% fetal bovine serum, streptomycin (100 μg/ml), penicillin (100 IU/ml), and Geneteicin (trade name, the antibiotic manufactured by Life Technologies, Co., Ltd., 0.2 mg/ml) at 37° C. The medium was changed with fresh medium on the second day and fifth day of the culture, and then the medium was changed with a medium containing a test serum at a final concentration of 5% (V/V) after 8, 11, and 14 days of the culture. Total cellular DNAs were collected on the 17th day of the culture. Amounts of the HBV-DNAs in the cells were measured by the Southern blotting method, and rates of inhibition of cytoplasmic HBV-DNA synthesis were determined. As a reference, a similar test was carried out using PMEA. Results are shown in Table 3.

                  TABLE 3                                                          ______________________________________                                                   Dose of oral   Inhibitory rate against                               Compound No.                                                                             administration (g/kg)                                                                         HBV-DNA synthesis (%)                                 ______________________________________                                         No. 1     0.3            60.7                                                  No. 4     0.3            95.2                                                  PMEA      1.0            35.5                                                  ______________________________________                                    

From the foregoing explanations, it is apparent that the phosphonate nucleotide compounds of the present invention have excellent antiviral activity, and moreover, high oral absorbability and high safety to living bodies. Therefore, they are expected to be useful as ingredients of medicaments. 

What is claimed is:
 1. A phosphonate nucleotide compound represented by the following formula (I) or its salt, or a hydrate or a solvate thereof: ##STR8## wherein R¹ represents hydrogen atom or a C₁ -C₆ alkoxy group, R² and R³ independently represent hydrogen atom, a C₁ -C₂ 2 alkyl group, an acyloxymethyl group, an acylthioethyl group, or an ethyl group substituted with one or more halogen atoms; R⁴ represents hydrogen atom, a C₁ -C₄ alkyl group, a C₁ -C₄ hydroxyalkyl group, or a C₁ -C₄ alkyl group substituted with one or more halogen atoms; and X represents a carbon atom or a nitrogen atom.
 2. The phosphonate nucleotide compound or its salt, or a hydrate or a solvate thereof according to claim 1, wherein R¹ represents hydrogen atom or a C₁ -C₄ alkoxy group; and R² and R³ independently represent hydrogen atom, a C₁ -C₂ 2 alkyl group, or an ethyl group substituted with one or more halogen atoms.
 3. The phosphonate nucleotide compound or its salt, or a hydrate or a solvate thereof according to claim 1, wherein R¹ represents hydrogen atom or a C₁ -C₄ alkoxy group; R² and R³ independently represent hydrogen atom, a C₁ -C₂ 2 alkyl group, or 2,2,2-trifluoroethyl group; and R⁴ represents hydrogen atom or methyl group.
 4. The phosphonate nucleotide compound or its salt, or a hydrate or a solvate thereof according to claim 1, wherein R¹ represents hydrogen atom or a C₁ -C₄ alkoxy group; R² and R³ independently represent hydrogen atom or 2,2,2-trifluoroethyl group; and R⁴ represents hydrogen atom or methyl group.
 5. The phosphonate nucleotide compound or its salt, or a hydrate or a solvate thereof according to claim 4, which is selected from the group consisting of:2-amino-9- 2- bis(2,2,2-trifluoroethyl)phosphonylmethoxy!ethyl!-6-phenylthiopurine; 2-amino-9- 2- bis(2,2,2-trifluoroethyl)phosphonylmethoxy!ethyl!-6-p-methoxyphenylthiopurine; 2-amino-9- 2- bis(2,2,2-trifluoroethyl)phosphonylmethoxy!ethyl!-6-m-methoxyphenylthiopurine; 2-amino-9- 2- bis(2,2,2-trifluoroethyl)phosphonylmethoxy!ethyl!-6-o-methoxyphenylthiopurine; 2-amino-9- 2- bis(2,2,2-trifluoroethyl)phosphonylmethoxy!ethyl!-6-p-ethoxyphenylthiopurine; 2-amino-9- 2- bis(2,2,2-trifluoroethyl)phosphonylmethoxy!propyl!-6-phenylthiopurine; 2-amino-9- 2- bis(2,2,2-trifluoroethyl)phosphonylmethoxy!propyl!-6-p-methoxyphenylthiopurine; 2-amino-9- 2- (2,2,2-trifluoroethyl)phosphonylmethoxy!ethyl!-6-phenylthiopurine; 2-amino-9- 2- (2,2,2-trifluoroethyl)phosphonylmethoxy!ethyl!-6-p-methoxyphenylthiopurine; 2-amino-9- 2- phosphonylmethoxy!ethyl!-6-phenylthiopurine; 2-amino-9- 2- phosphonylmethoxy!ethyl!-6-p-methoxyphenylthiopurine; 2-amino-9- 2- bis(2,2,2-trifluoroethyl)phosphonylmethoxy!ethyl!-6-p-butoxyphenylthiopurine; 2-amino-9- 2- bis(2,2,2-trifluoroethyl)phosphonylmethoxy!ethyl!-6-p-propoxyphenylthiopurine; 2-amino-9- 2-(bis(2,2,2-trifluoroethyl)phosphonylmethoxy!ethyl!-6-p-isopropoxyphenylthiopurine; and 2-amino-9- 2- bis(2,2,2-trifluoroethyl)phosphonylmethoxy!ethyl!-6-p-isobutoxyphenylthiopurine.
 6. The phosphonate nucleotide compound or its salt, or a hydrate or a solvate thereof according to claim 1, wherein R¹ is hydrogen atom or a C₁ -C₄ alkoxy group; R² and R³ represent 2,2,2-trifluoroethyl group; and R⁴ represents hydrogen atom or methyl group.
 7. The phosphonate nucleotide compound or its salt, or a hydrate or a solvate thereof according to claim 6, which is selected from the group consisting of:2-amino-9- 2- bis(2,2,2-trifluoroethyl)phosphonylmethoxy!ethyl!-6-phenylthiopurine; 2-amino-9- 2- bis(2,2,2-trifluoroethyl)phosphonylmethoxy!ethyl!-6-p-methoxyphenylthiopurine; 2-amino-9- 2- bis(2,2,2-trifluoroethyl)phosphonylmethoxy!ethyl!-6-m-methoxyphenylthiopurine; 2-amino-9- 2- bis(2,2,2-trifluoroethyl)phosphonylmethoxy!ethyl!-6-o-methoxyphenylthiopurine; 2-amino-9- 2- bis(2,2,2-trifluoroethyl)phosphonylmethoxy!ethyl!-6-p-ethoxyphenylthiopurine; 2-amino-9- 2- bis(2,2,2-trifluoroethyl)phosphonylmethoxy!propyl!-6-phenylthiopurine; 2-amino-9- 2- bis(2,2,2-trifluoroethyl)phosphonylmethoxy!propyl!-6-p-methoxyphenylthiopurine; 2-amino-9- 2- bis(2,2,2-trifluoroethyl)phosphonylmethoxy!ethyl!-6-p-butoxyphenylthiopurine; 2-amino-9- 2- bis(2,2,2-trifluoroethyl)phosphonylmethoxy!ethyl!-6-p-propoxyphenylthiopurine; 2-amino-9- 2- bis(2,2,2-trifluoroethyl)phosphonylmethoxy!ethyl!-6-p-isopropoxyphenylthiopurine; and 2-amino-9- 2- bis(2,2,2-trifluoroethyl)phosphonylmethoxy!ethyl!-6-p-isobutoxyphenylthiopurine.
 8. The phosphonate nucleotide compound or its salt, or a hydrate or a solvate thereof according to claim 1, wherein R¹ is hydrogen atom or a C₁ -C₄ alkoxy group; R² and R³ represent 2,2,2-trifluoroethyl group; and R⁴ represents hydrogen atom.
 9. The phosphonate nucleotide compound or its salt, or a hydrate or a solvate thereof according to claim 8, which is selected from the group consisting of:2-amino-9- 2- bis(2,2,2-trifluoroethyl)phosphonylmethoxy!ethyl!-6-phenylthiopurine; 2-amino-9- 2- bis(2,2,2-trifluoroethyl)phosphonylmethoxy!ethyl!-6-p-methoxyphenylthiopurine; 2-amino-9- 2- bis(2,2,2-trifluoroethyl)phosphonylmethoxy!ethyl!-6-m-methoxyphenylthiopurine; 2-amino-9- 2- bis(2,2,2-trifluoroethyl)phosphonylmethoxy!ethyl!-6-o-methoxyphenylthiopurine; 2-amino-9- 2- bis(2,2,2-trifluoroethyl)phosphonylmethoxy!ethyl!-6-p-ethoxyphenylthiopurine; 2-amino-9- 2- bis(2,2,2-trifluoroethyl)phosphonylmethoxy!ethyl!-6-p-butoxyphenylthiopurine; 2-amino-9- 2- bis(2,2,2-trifluoroethyl)phosphonylmethoxy!ethyl!-6-p-propoxyphenylthiopurine; 2-amino-9- 2- bis(2,2,2-trifluoroethyl)phosphonylmethoxy!ethyl!-6-p-isopropoxyphenylthiopurine; and 2-amino-9- 2- bis(2,2,2-trifluoroethyl)phosphonylmethoxy!ethyl!-6-p-isobutoxyphenylthiopurine.
 10. The phosphonate nucleotide compound or its salt, or a hydrate or a solvate thereof according to claim 1, wherein R¹ represents hydrogen atom or a C₁ -C₂ alkoxy group; R² and R³ represent 2,2,2-trifluoroethyl group; and R⁴ represents hydrogen atom.
 11. The phosphonate nucleotide compound or its salt, or a hydrate or a solvate thereof according to claim 1, wherein the compound is 2-amino-9- 2- bis(2,2,2-trifluoroethyl)phosphonylmethoxy!ethyl!-6-phenylthiopurine.
 12. The phosphonate nucleotide compound or its salt, or a hydrate or a solvate thereof according to claim 1, wherein the compound is 2-amino-9- 2- bis(2,2,2-trifluoroethyl)phosphonylmethoxy!ethyl!-6-p-methoxyphenylthiopurine.
 13. The phosphonate nucleotide compound or its salt, or a hydrate or a solvate thereof according to claim 1, wherein the compound is 2-amino-9- 2- bis(2,2,2-trifluoroethyl)phosphonylmethoxy!ethyl!-6-m-methoxyphenylthiopurine.
 14. The phosphonate nucleotide compound or its salt, or a hydrate or a solvate thereof according to claim 1, wherein the compound is 2-amino-9- 2- -(bis(2,2,2-trifluoroethyl)phosphonylmethoxy!ethyl!-6-o-methoxyphenylthiopurine.
 15. The phosphonate nucleotide compound or its salt, or a hydrate or a solvate thereof according to claim 1, wherein the compound is 2-amino-9- 2- bis(2,2,2-trifluoroethyl)phosphonylmethoxy!ethyl!-6-p-ethoxyphenylthiopurine.
 16. A pharmaceutical composition comprising a substance selected from the group of the phosphonate nucleotide compound and its salt, and a hydrate and a solvate thereof according to claim 1 together with a pharmaceutically acceptable additive.
 17. A method for the treatment of a viral infection which comprises administering to a patient in need of such treatment an effective amount of a substance selected from the group of the phosphonate nucleotide compound and its salt, and a hydrate and a solvate thereof as defined in claim I.
 18. A method according to claim 17 wherein the virus is hepatitis B virus. 